Loss of MCT1, MCT3, and MCT4 expression in the retinal pigment epithelium and neural retina of the 5A11/basigin-null mouse

Invest Ophthalmol Vis Sci. 2003 Mar;44(3):1305-11. doi: 10.1167/iovs.02-0552.

Abstract

Purpose: The neural retina expresses multiple monocarboxylate transporters (MCTs) that are likely to play a key role in the metabolism of the outer retina. Recently, it was reported that targeting of MCT1 and -4 to the plasma membrane requires association with 5A11/basigin (CD147). In the present study, the hypothesis that reduced amplitudes in the electroretinograms in the 5A11/basigin null mouse (Bsg(-/-)) may be linked to altered expression of MCTs was studied.

Methods: The expression and subcellular distribution of MCTs in Bsg(-/-) mice was analyzed by immunofluorescence microscopy with isoform-specific antibodies. Protein expression was analyzed by Western blot analysis, and mRNA expression was examined with RT-PCR.

Results: Immunofluorescence labeling of tissue sections from the Bsg(-/-) mice revealed a dramatic reduction in labeling with MCT antibodies. There was a loss of MCT1 labeling in the apical membrane of the RPE and in the neural retina. MCT3, which is expressed in the basolateral membrane of the RPE wild-type mouse, was expressed at very low levels in both the apical and basolateral membranes of the Bsg(-/-) mouse. There was no change in expression or distribution of the glucose transporter (GLUT)-1 in the RPE and retina of the Bsg(-/-) mouse. Western blot analysis of detergent-soluble lysates prepared from wild-type and Bsg(-/-) eyes confirmed that the levels of MCT1, MCT3, and MCT4 protein were severely reduced in Bsg(-/-) mice. RT-PCR analyses of mRNA levels from wild-type and Bsg(-/-) mice demonstrated that the MCT1 transcript was expressed at normal levels in Bsg(-/-) mice.

Conclusions: In Bsg(-/-) mice, there is a severe reduction in accumulation of the MCT1 and -3 proteins in the RPE and a concomitant reduction in MCT1 and -4 in the neural retina supporting a role for 5A11/basigin in the targeting of these transporters to the plasma membrane. Decreased expression of MCT1 and -4 on the surfaces of Müller and photoreceptor cells may compromise energy metabolism in the outer retina, leading to abnormal photoreceptor cell function and degeneration.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD*
  • Antigens, Neoplasm*
  • Antigens, Surface*
  • Avian Proteins*
  • Basigin
  • Blood Proteins*
  • Blotting, Western
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Fluorescent Antibody Technique, Indirect
  • Gene Deletion
  • Membrane Glycoproteins / physiology*
  • Membrane Transport Proteins
  • Mice
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Monocarboxylic Acid Transporters / genetics
  • Monocarboxylic Acid Transporters / metabolism*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Pigment Epithelium of Eye / metabolism*
  • Pigment Epithelium of Eye / pathology
  • RNA, Messenger / metabolism
  • Retina / metabolism*
  • Retina / pathology
  • Retinal Degeneration / genetics
  • Retinal Degeneration / metabolism*
  • Retinal Degeneration / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Symporters / genetics
  • Symporters / metabolism*

Substances

  • Antigens, CD
  • Antigens, Neoplasm
  • Antigens, Surface
  • Avian Proteins
  • Blood Proteins
  • Bsg protein, Gallus gallus
  • Bsg protein, mouse
  • Bsg protein, rat
  • Carrier Proteins
  • Mct3 protein, rat
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Monocarboxylic Acid Transporters
  • Muscle Proteins
  • RNA, Messenger
  • Slc16a3 protein, mouse
  • Slc16a4 protein, mouse
  • Symporters
  • monocarboxylate transport protein 1
  • Basigin