Loss of MCT1, MCT3, and MCT4 Expression in the Retinal Pigment Epithelium and Neural Retina of the 5A11/Basigin-Null Mouse

Philp, Nancy J.; Ochrietor, Judith D.; Rudoy, Carla; Muramatsu, Takashi; Linser, Paul J.

doi:10.1167/iovs.02-0552

Cited by 204 publications

(241 citation statements)

References 34 publications

(46 reference statements)

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“…What connects the extracellular Ig domain 2 of CD147 to caveolin-1, an integral membrane protein? One possibility is CD147-associated multimembrane spanning monocarboxylate transporters MCT1 and MCT4 (27,43). However, replacement of the CD147 transmembrane domain would be expected to eliminate MCT association because of loss of a required membrane-embedded glutamic acid (44), but our replacements of the CD147 transmembrane domain did not eliminate caveolin-1 association.…”

mentioning

confidence: 97%

Caveolin-1 Regulates Matrix Metalloproteinases-1 Induction and CD147/EMMPRIN Cell Surface Clustering

Tang

Hemler

2004

Journal of Biological Chemistry

137

125

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CD147, a regulator of matrix metalloproteinase (MMP) production, showed highly specific association with caveolin-1 on the surface of multiple cell types. CD147-caveolin-1 complex formation was temperature and cholesterol dependent, reminiscent of associations seen within caveolae/lipid rafts. However, the subset of caveolin-1 associated with CD147 appeared exclusively within intermediate density sucrose gradient fractions, rather than in the low density fractions containing the bulk of caveolin-1. Mutagenesis experiments revealed that CD147 Ig domain 2 was required for caveolin-1 association. In contrast to CD147-caveolin-1 complexes, CD147-␣ 3 integrin association was not disrupted upon cholesterol depletion, occurred in high density sucrose fractions, and did not involve CD147 Ig domain 2. Overexpression of caveolin-1 caused a specific decrease in clustering of cell surface CD147, as detected by "cluster specific" mAb M6/13. Conversely, a mutant CD147 deficient in caveolin-1 association showed enhanced spontaneous cell surface clustering (detected by mAb M6/13), and did not show decreased clustering in response to caveolin-1 overexpression. Furthermore, the same CD147 mutant yielded an elevated induction of MMP-1. In conclusion, caveolin-1 associates with CD147, in a complex distinct from CD147-␣ 3 integrin complexes, thereby diminishing both CD147 clustering and CD147-dependent MMP-1-inducing activity.Stromal fibroblasts secrete multiple matrix metalloproteinases (MMP) 1 that can promote tumor cell growth, survival, invasion, angiogenesis, and metastasis (1-3). A search for MMP-inducing tumor cell factors led to discovery and characterization of CD147/EMMPRIN (4,5). This molecule, on the surface of carcinoma cells or in recombinant soluble form, stimulates production of MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), and MMP-3 (stromelysin) but not TIMP-1 (4 -7). The name "EMMPRIN" reflects the extracellular matrix metalloproteinase inducer activity of CD147. CD147 expression is often elevated on human tumor cells (4,8,9) and correlates with glioma tumor progression (10), hepatoma metastasis (11), and squamous cell carcinoma invasion, MMP-2 production, and extracellular matrix degradation (12). On melanoma cells, elevated CD147 promotes MMP-1, MMP-2, and MMP-3 production, and invasion through basement membrane (13,14), whereas overexpression of CD147 in a breast cancer cell line stimulated MMP-2 and MMP-9 production, and tumor growth and metastasis in nude mice (15). In summary, CD147 on tumor cells stimulates MMP production by stromal cells and/or other tumor cells, thereby leading to extracellular matrix degradation, and elevated tumor growth and metastasis. The MMP-inducing functions of CD147 at least partly involve CD147 acting as a counter-receptor for itself (16).Also, CD147 stimulates production of MMP-1 and MMP-3 in rheumatoid synovial tissue (17), and may facilitate erythrocyte circulation (18), and development of the thymus (19) and retina (20). Mice lacking the gene for CD147/EMMPRIN (call...

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mentioning

confidence: 97%

Caveolin-1 Regulates Matrix Metalloproteinases-1 Induction and CD147/EMMPRIN Cell Surface Clustering

Tang

Hemler

2004

Journal of Biological Chemistry

137

125

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“…Very little is known about the mechanisms that regulate the polarized distribution of many key metabolite transporters that, like P-type ATPases, anion, monocarboxylate, and L-amino acid transporters, are multispan nonglycosylated proteins. Many of these metabolite transporters require dimerization with a single span type I or II glycoprotein for surface expression (4)(5)(6)(7)(8)(9). Only in the case of Na ϩ ,K ϩ -ATPase and H ϩ ,K ϩ -ATPase it is known that sorting information for polarized delivery is present in the nonglycosylated, catalytic ␣-subunit (4).…”

mentioning

confidence: 99%

“…Of 14 known family members, only MCT1-MCT4 are well characterized; they share 40-60% homology and have distinct tissue distribution and lactate͞ proton transport kinetics (15,16). MCT1, MCT3, and MCT4 associate with CD147 (9,12,17), a ubiquitous type I single-span transmembrane glycoprotein of the Ig superfamily (18). MCT2 was recently found to associate with GP70, a homolog of CD147 (19).…”

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confidence: 99%

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Mechanisms regulating tissue-specific polarity of monocarboxylate transporters and their chaperone CD147 in kidney and retinal epithelia

Deora

Philp²,

Hu³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

126

121

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Proton-coupled monocarboxylate transporters (MCT) MCT1, MCT3, and MCT4 form heterodimeric complexes with the cell surface glycoprotein CD147 and exhibit tissue-specific polarized distributions that are essential for maintaining lactate and pH homeostasis. In the parenchymal epithelia of kidney, thyroid, and liver, MCT͞CD147 heterocomplexes are localized in the basolateral membrane where they transport lactate out of or into the cell depending on metabolic conditions. A unique distribution of lactate transporters is found in the retinal pigment epithelium (RPE), which regulates lactate levels of the outer retina. In RPE, MCT1͞ CD147 is polarized to the apical membrane and MCT3͞CD147 to the basolateral membrane. The mechanisms responsible for tissuespecific polarized distribution of MCTs are unknown. Here, we demonstrate that CD147 carries sorting information for polarized targeting of the MCT1͞CD147 hetero-complexes in kidney and RPE cells. In contrast, MCT3 and MCT4 harbor dominant sorting information that cotargets CD147 to the basolateral membrane in both epithelia. RNA interference experiments show that MCT1 promotes CD147 maturation. Our results open a unique paradigm to study the molecular basis of tissue-specific polarity.apical ͉ basolateral ͉ polarized epithelium

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“…EMMPRIN or CD147) and embigin (a.k.a. gp70) which are plasma membrane glycoproteins (Philp et al, 2003;Deora et al, 2005;Wilson et al, 2005). Loss of Bsg function results in decreases of MCT1, 3, and 4 expression in retina (Philp et al, 2003) and in altered distribution of MCT1 in the efferent ductules and muscle (Nakai et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Postnatal Ontogeny of Expression of Monocarboxylate Transporters(MCTs) and Two Regulatory Proteins, Basigin and Embigin, in The Epididymis of Male Rat

2008

Journal of Animal Science and Technology

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Loss of MCT1, MCT3, and MCT4 Expression in the Retinal Pigment Epithelium and Neural Retina of the 5A11/Basigin-Null Mouse

Cited by 204 publications

References 34 publications

Caveolin-1 Regulates Matrix Metalloproteinases-1 Induction and CD147/EMMPRIN Cell Surface Clustering

Caveolin-1 Regulates Matrix Metalloproteinases-1 Induction and CD147/EMMPRIN Cell Surface Clustering

Mechanisms regulating tissue-specific polarity of monocarboxylate transporters and their chaperone CD147 in kidney and retinal epithelia

Postnatal Ontogeny of Expression of Monocarboxylate Transporters(MCTs) and Two Regulatory Proteins, Basigin and Embigin, in The Epididymis of Male Rat

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