MAP17 Is a Necessary Activator of Renal Na+/Glucose Cotransporter SGLT2
| Autor: | Michael J. Coady, Abdulah El Tarazi, Pierre Bissonnette, Yoann Lussier, René Santer, Daniel G. Bichet, Jean-Yves Lapointe, Joaquim Calado, Christopher Dumayne, Louis J. Sasseville |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Scaffold protein Glycosuria Renal Kidney Kidney Tubules Proximal 03 medical and health sciences 0302 clinical medicine Sodium-Glucose Transporter 2 medicine Animals Humans Protein kinase A Cells Cultured Activator (genetics) Chemistry Glucose transporter Membrane Proteins Opossums General Medicine Molecular biology Renal glucose reabsorption Basic Research 030104 developmental biology medicine.anatomical_structure Nephrology 030220 oncology & carcinogenesis Mutation Expression cloning Signal transduction |
| Zdroj: | Journal of the American Society of Nephrology. 28:85-93 |
| ISSN: | 1533-3450 1046-6673 |
| DOI: | 10.1681/asn.2015111282 |
| Popis: | The renal proximal tubule reabsorbs 90% of the filtered glucose load through the Na+-coupled glucose transporter SGLT2, and specific inhibitors of SGLT2 are now available to patients with diabetes to increase urinary glucose excretion. Using expression cloning, we identified an accessory protein, 17 kDa membrane-associated protein (MAP17), that increased SGLT2 activity in RNA-injected Xenopus oocytes by two orders of magnitude. Significant stimulation of SGLT2 activity also occurred in opossum kidney cells cotransfected with SGLT2 and MAP17. Notably, transfection with MAP17 did not change the quantity of SGLT2 protein at the cell surface in either cell type. To confirm the physiologic relevance of the MAP17–SGLT2 interaction, we studied a cohort of 60 individuals with familial renal glucosuria. One patient without any identifiable mutation in the SGLT2 coding gene (SLC5A2) displayed homozygosity for a splicing mutation (c.176+1G>A) in the MAP17 coding gene (PDZK1IP1). In the proximal tubule and in other tissues, MAP17 is known to interact with PDZK1, a scaffolding protein linked to other transporters, including Na+/H+ exchanger 3, and to signaling pathways, such as the A-kinase anchor protein 2/protein kinase A pathway. Thus, these results provide the basis for a more thorough characterization of SGLT2 which would include the possible effects of its inhibition on colocalized renal transporters. |
| Databáze: | OpenAIRE |
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