Molecular Vision 2020; 26:652-660 <>
Received 06 June 2020 | Accepted 02 October 2020 | Published 04 October 2020

Review: Intraflagellar transport proteins in the retina

Chitra Kannabiran

Kallam Anji Reddy Molecular Genetics Laboratory, Prof Brien Holden Eye Research Centre, L.V. Prasad Eye Institute, Kallam Anji Reddy Campus, Hyderabad, India

Correspondence to: Chitra Kannabiran, Kallam Anji Reddy Molecular Genetics Laboratory, Prof Brien Holden Eye Research Centre, L.V. Prasad Eye Institute, Kallam Anji Reddy Campus, Hyderabad 500034, India; Phone: 91-40-30612507; FAX: 91-40-2354 8271; email:;


Intraflagellar transport (IFT) is an essential process in all organisms that serves to move proteins along flagella or cilia in either direction. IFT is performed by IFT particles, which are multiprotein complexes organized into two subcomplexes, A and B. The IFT proteins form interactions with each other, with cargo proteins, and with membranes during the transport process. Several IFT proteins are expressed in many parts of the retina, such as the outer plexiform and outer nuclear layers, and function in the transport of photoreceptor proteins between the inner and outer segments. Mutants of IFT protein genes have been characterized in model organisms such as Chlamydomonas, C. elegans, zebrafish, and the mouse. These mutants have defective ciliogenesis or abnormalities in retinal photoreceptors. Mutations in IFT genes are associated with syndromic and non-syndromic forms of retinal disease in humans, frequently with early onset of disease.


Cilia and flagella are appendages protruding from the cell surface that have a microtubule-based structure. Cilia are generally present in large numbers on the surface of cells and may perform either sensory or motile functions. Flagella are present as single units, are longer than cilia, and primarily function in locomotion. Cilia are of two types: motile cilia and non-motile or primary cilia. Motile cilia perform the task of moving fluids or substances through the organ, for example, cilia in the respiratory tract and fallopian tubes. Primary cilia, however, are present on all cells in mammals. Cilia are made up of doublets of microtubules, organized into an axoneme. The axoneme is surrounded by the plasma membrane. Motile cilia have an axoneme made up of nine microtubule doublets, containing the A and B types of microtubules, surrounding two singlet microtubules in the center (the 9 + 2 arrangement). Primary cilia contain nine microtubule doublets but lack the two central microtubules. The axoneme attaches to the cell surface through the basal body, which also consists of microtubules, present in triplets, containing A, B, and C types of microtubules. Only the A and B microtubules of the basal body continue into the shaft of the axoneme. The basal body is attached to the plasma membrane by protein fibers. The entire structure of the cilia or flagella is estimated to contain more than several hundred proteins, many of which are evolutionarily conserved [1]. The assembly of the axoneme by elongation of the microtubules at its tip necessitates the transport of axonemal subunits along the length of the cilium, from the base to the growing end. In addition, the absence of protein synthesis machinery in the cilia requires that ciliary proteins are made in the cytoplasm of the cell and transported to the cilium. Thus, the intraflagellar transport (IFT) processes serve to move the various protein complexes through the cilium. This is brought about by polymers of IFT particles, known as IFT trains, which are moved along the cilium. Anterograde transport of particles from the base to the tip of the cilium is performed along the microtubule doublets, to transport substances required for axoneme assembly. Retrograde transport serves to recycle IFT particles from the tip to the base of the cilium. Studies on Chlamydomonas mutants have suggested that movements of IFT particles are enabled by motor proteins, related to kinesin (heterotrimeric kinesin II) and dynein 2, for anterograde and retrograde transport, respectively [2].

Intraflagellar transport has several functions that are part of essential processes in all organisms. These functions are cell motility, cytokinesis, and sensory functions in organs such as the kidney and the retina, control of left-right asymmetry during development, cell mating, and control of flagellar length [3].


The IFT proteins

Analysis of IFT complexes from Chlamydomonas by purification of proteins from wild-type and mutant flagellae enabled the identification of the complexes with two-dimensional gel electrophoresis. There are two IFT subcomplexes, A and B, that are different in their subunit composition and in the functions that they perform (Figure 1A,B). The IFTB complex is involved in anterograde transport, and mutants lacking any of the proteins of the IFTB complex have shortened cilia. However, the IFTA complex functions in retrograde transport, and IFTA mutants have bulges in their cilia, which contain accumulated proteins [4,5]. The proteins in these IFT complexes are named after their molecular weights, although there are some differences in the components of complexes A and B as described by different authors, in terms of the specific polypeptides that have been designated in these complexes (Figure 1). According to a report by Taschner and coworkers [6], members of the IFTA complex are of high molecular weight (>100 kDa), namely, p144, p140, p139, and p122. For the IFTB complex, there are 11 subunits that are mostly of lower molecular weight (<100 kDa): IFT172, IFT88, IFT81, IFT80, IFT74/72, IFT57/55, IFT52, IFT46, IFT27, and IFT20. In high salt conditions, the dissociation of a few subunits that are more weakly bound, i.e., p172, p80, p57, and p20, from the IFTB complex leaves a salt-stable core complex made up of other nine subunits p88, p81, p74, p72, p52, p46, and p27 [6]. A somewhat similar composition of proteins, although with differences from the above, has also been described. In this configuration, the IFTA complex has six subunits (IFT144, IFT140, IFT139, IFT122, and IFT121) with p43 in addition. The IFTB complex is reported as having two subcomplexes: B1 (consisting of IFT88, IFT81, IFT74, IFT70, IFT56, IFT52, IFT46, IFT27, and IFT25, and IFT22), similar to the salt-stable core complex mentioned above, and B2 with six subunits (IFT172, IFT80, IFT57, IFT54, IFT38, and IFT20) consisting of weakly bound proteins [5,7]. The structure of the IFTB complex in mammalian cells has been elucidated with immunoprecipitation assays in mouse embryo fibroblasts [8].

Protein–protein interactions are crucial to the organization and functioning of the IFT proteins between members of a complex and between IFT complexes and their cargo proteins. Members of the IFTA complex possess interaction domains, such as the tetratricopeptide (TPR) domain, beta-propellers, – expansion of tryptophan-aspartic acid (WD) repeats, and coiled-coil domains [9]. Thus, it appears that the IFTA complex is primarily a structural entity that provides interaction surfaces with other proteins. Apart from protein interaction domains in members of the IFTA complex, interaction with membranes is a property of certain members such as the IFT172 protein, a part of the IFTB complex. IFT172 is capable of remodeling membranes into vesicles. Interaction of IFT172 with membranes appears to be through its N-terminal β-propeller domain [10]. Membrane interaction of IFT proteins may be required during the movement of IFT trains, which are located between the axoneme and the ciliary membrane. In the following sections, we discuss the effects of intraflagellar transport proteins in the retina.

Intraflagellar transport proteins in the retina

Expression of several IFT proteins has been observed in the connecting cilium of the photoreceptors, the inner segments, and the outer plexiform layers of the bovine retina [11]. Studies on the localization of the IFT88 protein in mouse and Xenopus retinas suggested that it is present in the basal body and centriole, and additionally, IFT88, IF57, IFT52, and IFT20 proteins are found throughout the length of the axoneme in Xenopus. Immunogold labeling of IFT88 in the mouse retina detected IFT88 in particulate or vesicular structures [12]. The kinesin 17 (Kif17) protein, which is the motor component of the IFT particles, was also found to be expressed in all layers of the zebrafish retina, and similar to the other IFT proteins, is found along the axoneme of rods and cones [13]. The IFT particles transport photoreceptor membrane proteins, such as rhodopsin and retinal guanylyl cyclase 1, between the inner and outer segments [14]. IFT complexes from bovine photoreceptors contain IFT88 in association with guanylate cyclase 1 (GC1), rhodopsin, and chaperone proteins, particularly the mammalian relative of DNAJ (the MRJ protein), detectable with yeast two-hybrid and pull-down assays [15]. IFT proteins are also expressed in post-synaptic dendritic terminals of bipolar and horizontal cells of the mammalian retina, as detected with immunoelectron microscopy [16].

Animal models for IFT mutants

Intraflagellar transport is critical to the transport of proteins between the inner and outer segments of photoreceptors through the connecting cilium. The association of retinal disease with mutations at several IFT loci attests to the importance of these proteins in the process of vision. Orthologs of the major IFT proteins found in Chlamydomonas are found in the human retina, within the connecting cilia. Mutations in most of the IFT complex genes are associated with defects in ciliogenesis or intraflagellar transport in model organisms, such as C. elegans, C. reinhardtii, Danio rerio (zebrafish), and Mus musculus (Table 1) [17].

The identification of a mutant mouse model, Tg737, which is an insertional mutant in the Ift88 (Gene ID 21821) gene, paved the way toward understanding the biologic role of IFT88. Tg737 was generated by an insertion event affecting one of its exons without any effect on the coding regions of the remaining exons. Thus, the mutation reduced the amount of protein without eliminating it and was hypomorphic [18]. The Tg737 strain of mice showed ciliary defects in the kidneys and the retina. The outer segments of the photoreceptors were disorganized and smaller than those of healthy controls. Photoreceptors were lost due to apoptotic cell death, and there was a gradual reduction in retinal thickness [11]. The effect of ift88 knockdown on the retina was also evident in an insertional mutation in zebrafish, and mutants developed an absence of outer segments within the first few days of fertilization.

Apart from ift88, other intraflagellar transport protein genes appear to be essential for normal photoreceptor function, as observed in the corresponding zebrafish mutants. Knockdown of ift172 led to similar changes as observed in ift88 mutants, with a loss of outer segments, while mutants of ift57 manifested with a milder phenotype of shortened outer segments and mislocalized rhodopsin [19,20]. A retinal dystrophy phenotype was also found in a zebrafish mutant in the ift122 gene (designated as jj263) created with ethyl nitrosourea (ENU)-induced mutagenesis. The jj263 strain had a nonsense mutation and manifested with early degeneration of photoreceptors leading to the absence of the outer nuclear layer, while the inner nuclear and ganglion cell layers were normal. In addition to the photoreceptor defects, the mutant fish had pronephric cysts within 6 dpf, and ciliary abnormalities in the hair cells of the inner ear [21]. Similar to other IFT mutants, the ift122 mutants showed mislocalized opsin and disorganization of the outer segments.

In addition to the zebrafish model for IFT172 knockout (mentioned above), a conditional knockout mouse model for the same gene (Ift172fl/fl iCre), showed similar defects in the retina. In this model, Cre recombinase was expressed under the control of the rhodopsin promoter, thus achieving knockout of Ift172 specifically in the outer nuclear layer. Knockout mice showed mislocalization of rod outer segment proteins and early-onset retinal degeneration that closely followed the loss of Ift172 expression [22]. These defects in opsin localization have been observed with conditional knockout of Ift20 and Ift140 as well, and the mutants had opsins accumulating in the inner segments and the synapses, with gradual degeneration of cones [23,24].

The IFT38 (Gene ID 23059; OMIM 616787) gene encodes the clusterin-associated protein 1 (CLUAP1) that is part of the IFTB complex in vertebrates. Animal models such as the mouse and zebrafish with knockout of the Cluap1 gene had multiple defects due to the lack of primary cilia. Homozygous knockout mice (Cluap1−/−) showed embryonic lethality after 10 dpf. The knockout mouse embryos before 10 dpf showed loss of sonic hedgehog (Shh) activity, as well as a marked decrease in the expression of other targets of Shh (Patched1 and Gli1) [25]. A zebrafish recessive mutant strain au5 carries a nonsense mutation at amino acid 41 of Cluap1, thus truncating the protein in the N-terminal part. The phenotype of the au5 mutant strain includes curvature in the body axis, microphthalmia, and abnormal photoreceptors that lack cilia and eventually, degenerated within a few days post-fertilization [26] (see Table 1).

Mutations in IFT genes in retinal disease

There are several genes encoding intraflagellar transport proteins that have been found to have mutations in patients with retinal dystrophies, including syndromic and non-syndromic retinal dystrophy. However, data reported thus far suggests that the mutations in each of these genes are exceedingly rare in the populations tested, with about one mutation-positive patient per 500–1,000 patients, selected for the relevant ciliopathy phenotypes. A common feature among individuals with mutations in any of the IFT genes as described below was the early onset of the disease, within the first few years of life.

Mutations in specific IFT genes occur in patients with syndromic and non-syndromic disease involving different types of retinal dystrophy. A missense change (c.296G>A; pCys99Tyr) in the IFT27 (Gene ID 11020; OMIM 615870) gene (known as the BBS19 locus) was identified in a consanguineous Saudi family who had two siblings affected with Bardet-Biedl Syndrome (BBS), both homozygous for this mutation. The affected siblings were in their second decade and manifested with polydactyly, obesity, intellectual disability, renal failure, and retinitis pigmentosa. The pathogenicity of the Cys99Tyr change was confirmed by failure of the mutant transcript to rescue the phenotype of Ift27 morpholino-treated zebrafish [27]. Mutations in IFT27 have also been reported in other patients with BBS. Compound heterozygosity for mutations c.104A>G (Tyr35Cys) and a splice site change c.350–2A>G were identified in a patient with typical features of BBS, by targeted next generation sequencing (NGS) with a custom gene panel [28]. In a later report of a patient with BBS, whole exome analysis detected compound heterozygosity for mutations of c.104A>G (Tyr35Cys), and c.349 +1G>T [29]. Prenatal mortality has been observed in cases of severe ciliopathies that are due to mutations in IFT27. Compound heterozygous mutations of severe impact-c.118_125del, p.(Thr40Glyfs*11) and a c.352 +1G > T were detected in a fetus with a renal agenesis, short ribs, polydactyly, and imperforate anus. This phenotype shows overlap with Pallister-Hall syndrome [30].

Another syndromic retinal dystrophy of the rod-cone type is associated with mutations in the IFT81 (Gene ID 28981, OMIM 605489) gene: A deletion (c.2015_2019del (p.Asp672Alafs*15) mutation in IFT81 was reported in a proband with early-onset rod-cone dystrophy and cerebellar atrophy. The deletion predicted the loss of the stop codon and extension of the reading frame by ten amino acids. In a second proband with a similar syndromic disease in this study, no retinal disease was evident on the fundus evaluation, although the patient had polydactyly, intellectual disability, and nephronophthisis. The mutation identified in this case was c.1188 +1G>A, involving a conserved splice site [31]. In contrast to the above, compound heterozygous mutations consisting of a missense mutation (Leu614Pro) and a nonsense mutation (Arg405Ter) in the IFT81 gene were detected in a patient with non-syndromic early onset cone-rod dystrophy. The clinical features were reduced vision and photophobia in childhood, and loss of color vision [32].

Different ciliopathy phenotypes comprising syndromic and non-syndromic disease have been reported in patients with mutations in the IFT172 (Gene ID 26160; OMIM 607386) gene. Two affected siblings with a BBS-like syndrome consisting of retinitis pigmentosa, obesity, and other systemic abnormalities were compound heterozygous for two mutations in IFT172, one splice and one missense variant (c.1525 −1G>A; c.4701C>A (p.His1567Gln)). Further, autosomal recessive non-syndromic RP in two separate isolated cases was associated with missense (c.4815T>G; Asp1605Glu) or with compound heterozygosity for missense (c.770T>C; p.Leu257Pro) and splice (c.3112–5T>A) mutations, respectively, in IFT172 [33].

Apart from the disorders mentioned above, mutations in IFT genes are associated with different forms of LCA. A proband from Saudi Arabia affected with LCA had visual acuity of light perception and nystagmus at 6 weeks of age. No systemic defects were noted. A C>T substitution in the clusterin-associated protein 1 (CLUAP1) gene (Gene ID 23059, OMIM 616787) was identified with whole exome sequencing, as the molecular basis for the disease. This change, which predicts a substitution of phenylalanine for leucine, is designated as either c.817C>T or c.319C>T depending on whether the long or short isoforms of CLUAP1 are considered, respectively. Thus, it may lead to a missense change of either Leu273Phe or Leu107Phe [34]. Syndromic LCA has also been associated with a mutation in the IFT52 (Gene ID 51098, OMIM 617094) gene, consisting of c.556A>G leading to a missense substitution (pThr186Ala), discovered with whole genome sequencing. The disease in this patient manifested with severe visual loss from birth, eye rubbing and eye poking signs, mental retardation, growth retardation, and skeletal defects. The pThr186Ala mutation was predicted to be damaging to the protein. In vitro, the mutation appeared to lower the stability of the protein and decrease the length of the cilia in the transfected cell lines [35].

Analysis of non-syndromic, early-onset rod-cone degeneration in a consanguineous Pakistani family with multiple members identified mutations in the IFT43 (Gene ID 112752, OMIM 614068) gene. The mutation c.100G>A (p.Glu34Lys) in IFT43 cosegregated with the disease in the family and was absent in various healthy populations [36]. The patients had night blindness by 5 years of age, disc pallor, attenuated vessels, and pigmentary deposits within the retina. The mutation caused defects in the cilia of cells transfected with the mutant gene, with possible aggregation of the protein.

The involvement of the IFT88 (Gene ID 8100, OMIM 600595) gene in human retinal disease was confirmed with the detection of compound heterozygosity for a nonsense mutation and a missense mutation (Arg266Ter (c796C>T) and Ala568Thr (c.1702G>A)) in two siblings with rod-cone dystrophy, with whole genome sequencing. These mutations were also shown to result in defective or absent cilia when expressed in genome-edited HeLa cells [37]. An apparent difference in the phenotypes in these patients was the age of onset of the disease, which was in the second to third decades of life, unlike the cases with mutations in other IFT genes discussed. This feature does not correlate with the nature of the mutations found among all these cases, which include stop and missense changes.

In addition, pathogenic changes in the IFT140 (Gene ID 9742, OMIM 614620) gene have been reported in families of Han Chinese and European ethnicity with non-syndromic RP and LCA [38]. These changes included various missense and frameshift mutations identified in seven families. In one proband with typical features of RP, compound heterozygosity of missense and frameshift changes (c.T4196C (p. Leu1399Pro) and c. 1898_1901delATAA (p. Asn633Sfs*10)) were found. Another patient with adult-onset RP was compound heterozygous for missense mutations Gly1276Arg and Cys663Trp. A patient with LCA had missense changes of Thr484Met and Cys329Arg. The remaining patients studied were also compound heterozygous for mutations in IFT140.

Mutations in the KIF3B (Gene ID 9371, OMIM 603754) subunit of the heterotrimeric kinesin-2, the motor component of IFT, were recently reported in a syndromic ciliopathy in two families. Exome sequencing revealed a substitution of c.748G>C leading to missense mutation Glu250Gln in a heterozygous proband with retinitis pigmentosa, polydactyly, and hepatic fibrosis. In addition, a second missense change Leu523Pro (c.1568T>C) was identified in a second family with retinitis pigmentosa. Expression of these mutant transcripts in zebrafish led to the retention of rhodopsin in the inner segment of the photoreceptor (PR), with an increase in ciliary length [39].

Conclusion and remaining questions

The IFT proteins impact a variety of sensory and motor processes through ciliary transport. In addition, these proteins are involved in cellular processes other than transport. For example, IFT188 affects mitosis, and alterations in the expression of this gene lead to deregulation of cell proliferation. Another IFT protein, IFT20, is involved in recycling of T-cell receptors. IFT20 also functions in the Golgi, in the sorting of ciliary proteins [6]. The IFT proteins may also mediate vesicular transport particularly in relation to the Golgi apparatus. IFT20 has been observed to colocalize with the post-Golgi transport vesicles in photoreceptors, secondary neurons, and non-neuronal cells of the retina [16]. These observations suggest a variety of functions performed by the IFT proteins, and these aspects need to be explored further to understand the whole spectrum of their physiologic actions. IFT proteins have been detected in non-ciliary parts of the retina, suggesting that these proteins could have non-ciliary functions. Other critical gaps in this field are in the determination of the factors involved in controlling the length of cilia, which grow to a defined extent during ciliary growth and regeneration. There are yet many unanswered questions regarding which factors control ciliary length [40]. An emerging facet of IFT proteins is their participation in the regulation of autophagy, which is linked to ciliogenesis, and in the modulation of the lysosomal pathway. These effects on lysosomal degradation and autophagy, as observed in an Ift20 knockout mouse model, in turn, impair the recycling of endosome-associated T-cell receptors and have wider effects on the differentiation of T-cells. These findings ascribe a role for IFT20 in controlling immune responses as well [41,42]. Knowledge of these and other biologic effects of the IFT proteins will help to further unravel the pathogenic basis of the associated diseases.


This work was supported by the Hyderabad Eye Research Foundation and by a grant from the Department of Biotechnology, Government of India.


  1. Pazour GJ, Agrin N, Leszyk J, Witman GB. Proteomic analysis of a eukaryotic cilium. J Cell Biol. 2005; 170:103-13. [PMID: 15998802]
  2. Rosenbaum JL, Witman GB. Intraflagellar transport. Nat Rev Mol Cell Biol. 2002; 3:813-25. [PMID: 12415299]
  3. Scholey JM. Intraflagellar transport. Annu Rev Cell Dev Biol. 2003; 19:423-43. [PMID: 14570576]
  4. Cole DG, Diener DR, Himelblau AL, Beech PL, Fuster JC, Rosenbaum JL. Chlamydomonas kinesin-II-dependent intraflagellar transport (IFT): IFT particles contain proteins required for ciliary assembly in Caenorhabditis elegans sensory neurons. J Cell Biol. 1998; 141:993-1008. [PMID: 9585417]
  5. Cole DG. The intraflagellar transport machinery of Chlamydomonas reinhardtii. Traffic. 2003; 4:435-42. [PMID: 12795688]
  6. Taschner M, Bhogaraju S, Lorentzen E. Architecture and function of IFT complex proteins in ciliogenesis. Differentiation. 2012; 83:S12-22. [PMID: 22118932]
  7. Yang H, Huang K. Dissecting the vesicular trafficking function of IFT subunits. Front Cell Dev Biol. 2020; 7:352 [PMID: 32010685]
  8. Katoh Y, Terada M, Nishijima Y, Takei R, Nozaki S, Hamada H, Nakayama K. Overall Architecture of the Intraflagellar Transport (IFT)-B Complex Containing Cluap1/IFT38 as an Essential Component of the IFT-B Peripheral Subcomplex. J Biol Chem. 2016; 291:10962-75. [PMID: 26980730]
  9. Lechtreck KF. IFT-Cargo Interactions and Protein Transport in Cilia. Trends Biochem Sci. 2015; 40:765-78. [PMID: 26498262]
  10. Wang Q, Taschner M, Ganzinger KA, Kelley C, Villasenor A, Heymann M, Schwill P, Lorentzen E, Mizuno M. Membrane Association and Remodeling by Intraflagellar Transport Protein IFT172. Nat Commun. 2018; 9:4684 [PMID: 30409972]
  11. Pazour GJ, Baker SA, Deane JA, Cole DG, Dickert BL, Rosenbaum JL, Witman GB, Besharse JC. The intraflagellar transport protein, IFT88, is essential for vertebrate photoreceptor assembly and maintenance. J Cell Biol. 2002; 157:103-13. [PMID: 11916979]
  12. Luby-Phelps K, Fogerty J, Baker SA, Pazour GJ, Besharse JC. Spatial Distribution of intraflagellar transport proteins in vertebrate photoreceptors. Vision Res. 2008; 48:413-23. [PMID: 17931679]
  13. Insinna C, Pathak N, Perkins B, Drummond I, Besharse JC. The homodimeric kinesin, Kif17, is essential for vertebrate photoreceptor sensory outer segment development. Dev Biol. 2008; 316:160-70. [PMID: 18304522]
  14. Insinna C, Besharse JC. Intraflagellar transport and the sensory outer segment of photoreceptors. Dev Dyn. 2008; 237:1982-92. [PMID: 18489002]
  15. Bhowmick R, Li M, Sun J, Baker SA, Insinna C, Besharse JC. Photoreceptor IFT complexes containing chaperones, guanylyl cyclase 1, and rhodopsin. Traffic. 2009; 10:648-63. [PMID: 19302411]
  16. Sedmak T, Wolfrum U. Intraflagellar transport molecules in ciliary and non-ciliary cells of the retina. J Cell Biol. 2010; 189:171-86. [PMID: 20368623]
  17. Cole DG, Snell WJ. Snapshot: Intraflagellar transport. Cell. 2009; 137:784-784.e1. [PMID: 19450523]
  18. Moyer JH, Lee-Tischler MJ, Kwon HY, Schrick JJ, Avner ED, Sweeney WE, Godfrey VL, Cacheiro NL, Wilkinson JE, Woychik RP. Candidate gene associated with a mutation causing recessive polycystic kidney disease in mice. Science. 1994; 264:1329-33. [PMID: 8191288]
  19. Krock BL, Perkins BD. The Intraflagellar Transport Protein IFT57 is required for cilia maintenance and regulates IFT-particle-kinesin-II dissociation in vertebrate photoreceptors. J Cell Sci. 2008; 121:1907-15. [PMID: 18492793]
  20. Sukumaran S, Perkins BD. Early defects in photoreceptor outer segment morphogenesis in zebrafish ift57, ift88 and ift172 intraflagellar transport mutants. Vision Res. 2009; 49:479-89. [PMID: 19136023]
  21. Boubakri M, Chaya T, Hirata H, Kajimura N, Kuwahara R, Ueno A, Malicki J, Furukawa T, Omori Y. Loss of ift122, a retrograde intraflagellar transport (IFT) complex component, leads to slow, progressive photoreceptor degeneration due to inefficient opsin transport. J Biol Chem. 2016; 291:24465-74. [PMID: 27681595]
  22. Gupta PR, Pendse N, Greenwald SH, Leon M, Liu Q, Pierce EA, Bujakowska KM. Ift172 conditional knock-out mice exhibit rapid retinal degeneration and protein trafficking defects. Hum Mol Genet. 2018; 27:2012-24. [PMID: 29659833]
  23. Keady BT, Zheng Y, Pazour GJ. IFT20 is required for opsin trafficking and photoreceptor outer segment development. Mol Biol Cell. 2011; 22:921-30. [PMID: 21307337]
  24. Crouse JA, Lopes VS, Sanagustin JT, Keady BT, Williams DS, Pazour GJ. Distinct functions for IFT140 and IFT120 in opsin transport. Cytoskeleton (Hoboken). 2014; 71:302-10. [PMID: 24619649]
  25. Pasek RC, Berbari NF, Lewis WR, Kesterson RA, Yoder BK. Mammalian Clusterin associated protein 1 is an evolutionarily conserved protein required for ciliogenesis. Cilia. 2012; 1:20 [PMID: 23351563]
  26. Lee C, Wallingford JB, Gross JM. Cluap1 is essential for ciliogenesis and photoreceptor maintenance in the vertebrate eye. Invest Ophthalmol Vis Sci. 2014; 55:4585-92. [PMID: 24970261]
  27. Aldahmesh MA, Li Y, Alhashem A, Anazi S, Alkuraya H, Hashem M, Awaji AA, Sogaty S, Alkharashi A, Alzahrani S, Al Hazzaa SA, Xiong Y, Kong S, Sun Z, Alkuraya FS. IFT27, encoding a small GTPase component of IFT particles, is mutated in a consanguineous family with Bardet-Biedl syndrome. Hum Mol Genet. 2014; 23:3307-15. [PMID: 24488770]
  28. Sanchez-Navarro I. R J da Silva L, Blanco-Kelly F, Zurita O, Sanchez-Bolivar N, Villaverde C, Lopez-Molina MI, Garcia-Sandoval B, Tahsin-Swafiri S, Minguez P, Riveiro-Alvarez R, Lorda I, Sanchez-Alcudia R, Perez-Carro R, Valverde D, Liu Y, Tian L, Hakonarson H, Avila-Fernandez A, Corton M, Ayuso C. Combining targeted panel-based resequencing and copy-number variation analysis for the diagnosis of inherited syndromic retinopathies and associated ciliopathies. Sci Rep. 2018; 8:5285 [PMID: 29588463]
  29. Schaefer E, Delvallée C, Mary L, Stoetzel C, Geoffroy V, Marks-Delesalle C, Holder-Espinasse M, Ghoumid J, Dollfus H, Muller J. Identification and characterization of known biallelic Mutations in the IFT27 (BBS19) gene in a novel family with Bardet-Biedl syndrome. Front Genet. 2019; 10:21 [PMID: 30761183]
  30. Quélin C, Loget P, Boutaud L, Elkhartoufi N, Milon J, Odent S, Fradin M, Demurger F, Pasquier L, Thomas S, Attié-Bitach T. Loss of function IFT27 variants associated with an unclassified lethal fetal ciliopathy with renal agenesis. Am J Med Genet A. 2018; 176A:1610-3. [PMID: 29704304]
  31. Perrault I, Halbritter J, Porath JD, Gérard X, Braun DA, Gee HY, Fathy HM, Saunier S, Cormier-Daire V, Thomas S, Attié-Bitach T, Boddaert N, Taschner M, Schueler M, Lorentzen E, Lifton RP, Lawson JA, Garfa-Traore M, Otto EA, Bastin P, Caillaud C, Kaplan J, Rozet JM, Hildebrandt F. IFT81, encoding an IFT-B core protein, as a very rare cause of a ciliopathy phenotype. J Med Genet. 2015; 52:657-65. [PMID: 26275418]
  32. Dharmat R, Liu W, Ge Z, Sun Z, Yang L, Li Y, Wang K, Thomas K, Sui R, Chen R. IFT81 as a candidate gene for non-syndromic retinal degeneration. Invest Ophthalmol Vis Sci. 2017; 58:2483-90. [PMID: 28460050]
  33. Bujakowska KM, Zhang Q, Siemiatkowska AM, Liu Q, Place E, Falk MJ, Consugar M, Lancelot ME, Antonio A, Lonjou C, Carpentier W, Mohand-Saïd S, den Hollander AI, Cremers FP, Leroy BP, Gai X, Sahel JA, van den Born LI, Collin RW, Zeitz C, Audo I, Pierce EA. Mutations in IFT172 cause isolated retinal degeneration and Bardet-Biedl Syndrome. Hum Mol Genet. 2015; 24:230-42. [PMID: 25168386]
  34. Soens ZT, Li Y, Zhao L, Eblimit A, Dharmat R, Li Y, Chen Y, Naqeeb M, Fajardo N, Lopez I, Sun Z, Koenekoop RK, Chen R. Hypomorphic mutations identified in the candidate Leber congenital amaurosis gene CLUAP1. Genet Med. 2016; 18:1044-51. [PMID: 26820066]
  35. Chen X, Wang X, Jiang C, Xu M, Liu Y, Qi R, Qi X, Sun X, Xie P, Liu Q, Yan B, Sheng X, Zhao C. IFT52 as a novel candidate for ciliopathies involving retinal degeneration. Invest Ophthalmol Vis Sci. 2018; 59:4581-9. [PMID: 30242358]
  36. Biswas P, Duncan JL, Ali M, Matsui H, Naeem MA, Raghavendra PB, Frazer KA, Arts HH, Riazuddin S, Akram J, Hejtmancik JF, Riazuddin SA, Ayyagari R. A mutation in IFT43 causes non-syndromic recessive retinal degeneration. Hum Mol Genet. 2017; 26:4741-51. [PMID: 28973684]
  37. Chekuri A, Guru AA, Biswas P, Branham K, Borooah S, Soto-Hermida A, Hicks M, Khan NW, Matsui H, Alapati A, Raghavendra PB, Roosing S, Sarangapani S, Mathavan S, Telenti A, Heckenlively JR, Riazuddin SA, Frazer KA, Sieving PA, Ayyagari R. IFT88 mutations identified in individuals with non-syndromic recessive retinal degeneration result in abnormal ciliogenesis. Hum Genet. 2018; 37:447-58. [PMID: 29978320]
  38. Xu M, Yang L, Wang F, Li X, Wang H, Wang W, Ge Z, Wang K, Zhao L, Li H, Li Y, Sui R, Chen R. Mutations in human IFT140 cause non-syndromic retinal degeneration. Hum Genet. 2015; 134:1069-78.
  39. Cogné B, Latypova X, Senaratne LDS, Martin L, Koboldt DC, Kellaris G, Fievet L, Le Meur G, Caldari D, Debray D, Nizon M, Frengen E, Bowne SJ. 99 Lives Consortium, Cadena EL, Daiger SP, Bujakowska KM, Pierce EA, Gorin M, Katsanis N, Bézieau S, Petersen-Jones SM, Occelli LM, Lyons LA, Legeai-Mallet L, Sullivan LS, Davis EE, Isidor B. Mutations in the Kinesin-2 motor KIF3B cause an autosomal dominant ciliopathy. Am J Hum Genet. 2020; 106:893-904. [PMID: 32386558]
  40. Ishikawa H, Marshall WF. Intraflagellar transport and ciliary dynamics. Cold Spring Harb Perspect Biol. 2017; 9:a021998 [PMID: 28249960]
  41. Pampliega O, Orhon I, Patel B, Sridhar S, Díaz-Carretero A, Beau I, Codogno P, Satir BH, Satir P, Cuervo AM. Functional interaction between autophagy and ciliogenesis. Nature. 2013; 502:194-200. [PMID: 24089209]
  42. Finetti F, Capitani N, Baldari CT. Emerging roles of the intraflagellar transport system in the orchestration of cellular degradation pathways. Front Cell Dev Biol. 2019; 7:292 [PMID: 31803744]
  43. Takei R, Katoh Y, Nakayama K. Robust interaction of IFT70 with IFT52–IFT88 in the IFT-B complex is required for ciliogenesis. Biol Open. 2018; 7:bio033241 [PMID: 29654116]
  44. Lee E, Sivan-Loukianova E, Eberl DF, Kernan MJ. An IFT-A protein is required to delimit functionally distinct zones in mechanosensory cilia. Curr Biol. 2008; 18:1899-906. [PMID: 19097904]
  45. Hirano T, Katoh Y, Nakayama K. Intraflagellar transport-A complex mediates ciliary entry and retrograde trafficking of ciliary G protein-coupled receptors. Mol Biol Cell. 2017; 28:429-39. [PMID: 27932497]
  46. Cortellino S, Wang C, Wang B, Bassi MR, Caretti E, Champeval D, Calmont A, Jarnik M, Burch J, Zaret KS, Larue L, Bellacosa A. Defective ciliogenesis, embryonic lethality and severe impairment of the sonic hedgehog pathway caused by inactivation of the mouse complex A intraflagellar transport gene Ift122/Wdr10, partially overlapping with the DNA repair gene Med1/Mbd4. Dev Biol. 2009; 325:225-37. [PMID: 19000668]
  47. Zhu B, Zhu X, Wang L, Liang Y, Feng Q, Pan J. Functional exploration of the IFT-A complex and intraflagellar transport and ciliogenesis. PLoS Genet. 2017; 13:e1006627 [PMID: 28207750]
  48. Lee MS, Hwang KS, Oh HW, Ji-Ae K, Kim HT, Cho HS, Lee JJ, Yeong Ko J, Choi JH, Jeong YM, You KH, Kim J, Park DS, Nam KH, Aizawa S, Kiyonari H, Shioi G, Park JH, Zhou W, Kim NS, Kim CH. IFT46 plays an essential role in cilia development. Dev Biol. 2015; 400:248-57. [PMID: 25722189]
  49. Keady BT, Samtani R, Tobita K, Tsuchya M, San Agustin JT, Follit JA, Jonassen JA, Subramanian R, Lo CW, Pazour GJ. IFT25 links the signal-dependent movement of Hedgehog components to intraflagellar transport. Dev Cell. 2012; 22:940-51. [PMID: 22595669]
  50. Brown JM, Cochran DA, Craige B, Kubo T, Witman GB. Assembly of IFT trains at the ciliary base depends on IFT74. Curr Biol. 2015; 25:1583-93. [PMID: 26051893]
  51. Brazelton WJ, Amundsen CD, Silflow CD, Lefebvre PA. The bld1 mutation Identifies the chlamydomonas osm-6 homolog as a gene required for flagellar assembly. Curr Biol. 2001; 11:1591-4. [PMID: 11676919]
  52. Pazour GJ, Dickert BL, Vucica Y, Seeley ES, Rosenbaum JL, Witman GB, Cole DG. Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella. J Cell Biol. 2000; 151:709-18. [PMID: 11062270]
  53. Pathak N, Obara T, Mangos S, Liu Y, Drummond IA. The zebrafish Fleer gene encodes an essential regulator of cilia tubulin polyglutamylation. Mol Biol Cell. 2007; 18:4353-64. [PMID: 17761526]
  54. Ishikawa H, Ide T, Yagi T, Jiang X, Hirono M, Sasaki H, Yanagisawa H, Wemmer KA, Stainier DY, Qin H, Kamiya R, Marshall WF. TTC26/DYF13 is an intraflagellar transport protein required for transport of motility-related proteins into flagella. eLife. 2014; 3:e01566 [PMID: 24596149]
  55. Li J, Sun Z. Qilin is essential for cilia assembly and normal kidney development in zebrafish. PLoS One. 2011; 6:e27365 [PMID: 22102889]
  56. Marszalek JR, Liu X, Roberts EA, Chui D, Marth JD, Williams DS, Goldstein LSB. Genetic evidence for selective transport of opsin and arrestin by Kinesin-II in mammalian photoreceptors. Cell. 2000; 102:175-87. [PMID: 10943838]