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Role of myosin IIA motor protein in NHE3-mediated sodium reabsorption in renal proximal tubule

Grant number: 18/01235-5
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): March 01, 2018
Effective date (End): February 29, 2020
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Adriana Castello Costa Girardi
Grantee:Renato de Oliveira Crajoinas
Home Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated research grant:16/22140-7 - Molecular bases of renal tubular function and dysfunction, AP.TEM

Abstract

The Na+/H+ exchanger isoform 3 (NHE3) is a transport protein responsible for reabsorption of the majority of the filtered NaCl, NaHCO3 and, consequently, water, in renal proximal tubules. This transporter therefore plays an essential role regulating volume and acid-base homeostasis and determining blood pressure levels. The NHE3 activity modulation in response to stimuli is mediated by a number of molecular mechanisms, among them the redistribution of the transporter between the microdomains in the apical membrane of the proximal tubule. Although the physiological, pharmacological and pathophysiological importance of the subcellular distribution of NHE3 is very well established in the literature, the mechanisms involved in the translocation of this transporter from the base to the body of microvilli and vice versa remain unclear. Previously affinity chromatography and mass spectrometry experiments have shown that the myosin heavy chain type IIA, the motor protein involved in the transport of transporters to the plasma membrane, is physically associated with NHE3 in renal proximal tubules (unpublished data). Thus, this project aims to elucidate the molecular mechanisms involved in the redistribution of NHE3 between the proximal tubule microvilli in a situation of stimulation of sodium reabsorption in this segment of the nephron.