Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 45, Pages 16245-16250Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0504419102
Keywords
apical; basolateral; polarized epithelium
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Funding
- Intramural NIH HHS [Z01 EY000444] Funding Source: Medline
- NEI NIH HHS [EY012042, EY08538, R01 EY008538, EY00331, R56 EY012042, EY14307, F32 EY014307, P30 EY000331, R01 EY012042, R01 EY000444] Funding Source: Medline
- NIGMS NIH HHS [R01 GM034107, GM34107] Funding Source: Medline
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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, MCT/CD147 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 (RIDE), which regulates lactate levels of the outer retina. In RIPE, MCT1/ CD147 is polarized to the apical membrane and MCT3/CD147 to the basolateral membrane. The mechanisms responsible for tissue-specific polarized distribution of MCTs are unknown. Here, we demonstrate that CD147 carries sorting information for polarized targeting of the MCT1/CD147 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.
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