Mechanisms regulating tissue-specific polarity of monocarboxylate transporters and their chaperone CD147 in kidney and retinal epithelia.
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 (RPE), which regulates lactate levels of the outer retina. In RPE, 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.
Deora
Ami A
AA
Margaret M. Dyson Vision Research Institute, Weill Medical College of Cornell University, New York, NY 10021, USA.
Philp
Nancy
N
Hu
Jane
J
Bok
Dean
D
Rodriguez-Boulan
Enrique
E
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D051926:Basigin / Q000737:chemistry / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004285:Dogs; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D009928:Organ Specificity; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D051381:Rats; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D000099233:Monocarboxylate Transport Protein 1
D000251:Adenosine Triphosphatases; D051926:Basigin; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C491393:Mct3 protein, rat; C106260:SLC16A3 protein, human; C406962:SLC16A4 protein, human; C516342:Slc16a3 protein, rat; C035123:magnesium sodium ATPase