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.
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.
Authors: Ami A Deora; Diego Gravotta; Geri Kreitzer; Jane Hu; Dean Bok; Enrique Rodriguez-Boulan Journal: Mol Biol Cell Date: 2004-06-23 Impact factor: 4.138
Authors: Jennifer R Chao; Kaitlen Knight; Abbi L Engel; Connor Jankowski; Yekai Wang; Megan A Manson; Haiwei Gu; Danijel Djukovic; Daniel Raftery; James B Hurley; Jianhai Du Journal: J Biol Chem Date: 2017-06-14 Impact factor: 5.157
Authors: Mark G Slomiany; G Daniel Grass; Angela D Robertson; Xiao Y Yang; Bernard L Maria; Craig Beeson; Bryan P Toole Journal: Cancer Res Date: 2009-01-27 Impact factor: 12.701
Authors: Neal S Peachey; Minzhong Yu; John Y S Han; Sylvain Lengacher; Pierre J Magistretti; Luc Pellerin; Nancy J Philp Journal: Adv Exp Med Biol Date: 2018 Impact factor: 2.622