Rat kidney MAP17 induces cotransport of Na-mannose and Na-glucose in Xenopus laevis oocytes.
Renal reabsorption is the main mechanism that controls mannose homeostasis. This takes place through a specific Na-coupled uphill transport system, the molecular identity of which is unknown. We prepared and screened a size-selected rat kidney cortex cDNA library through the expression of mannose transport in Xenopus laevis oocytes. We have identified a membrane protein that induces high-affinity and specific Na-dependent transport of d-mannose and d-glucose in X. laevis oocytes, most likely through stimulation of the capacity of an endogenous transport system of the oocyte. Sequencing has revealed that the cDNA encodes the counterpart of the human membrane-associated protein MAP17, previously known by its overexpression in renal, colon, lung, and breast carcinomas. We show that MAP17 is a 12.2-kDa nonglycosylated membrane protein that locates to the brush-border plasma membrane and the Golgi apparatus of transfected cells and that it is expressed in the proximal tubules of the kidney cortex and in the spermatids of the seminiferous tubules. It spans twice the cell membrane, with both termini inside the cell, and seems to form homodimers through intracellular Cys55, a residue also involved in transport expression. MAP17 is responsible for mannose transport expression in oocytes by rat kidney cortex mRNA. The induced transport has the functional characteristics of a Na-glucose cotransporter (SGLT), because d-glucose and alpha-methyl-d-glucopyranoside are also accepted substrates that are inhibited by phloridzin. The corresponding transporter from the proximal tubule remains to be identified, but it is different from the known mammalian SGLT-1, -2, and -3.
Blasco
Tatiana
T
Department of Toxicology, University of Zaragoza, Zaragoza E50013, Spain.
Aramayona
José J
JJ
Alcalde
Ana I
AI
Catalán
Julia
J
Sarasa
Manuel
M
Sorribas
Victor
V
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D001692:Biological Transport; D002460:Cell Line; D005260:Female; D006056:Golgi Apparatus / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008358:Mannose / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008871:Microvilli / Q000378:metabolism; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D009893:Opossums; D017433:Protein Structure, Secondary; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D014018:Tissue Distribution; D014982:Xenopus laevis
D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; D009363:Neoplasm Proteins; C509768:PDZK1IP1 protein, human; C509764:Pdzk1ip1 protein, rat; D012964:Sodium; D008358:Mannose