Project Details
Projekt
Physiological significance of the interaction between SLC26A3 and SLC26A6 with CFTR or NHE3 for secretion and absorption in the intestine
Applicants
Dr. Mahdi Amiri; Professor Dr. Hans Georg Lamprecht
Subject Area
Anatomy and Physiology
Term
since 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 426950122
SLC26A3 and SLC26A6 are closely related bona fide Cl/HCO3 exchangers that contribute in the intestine to bicarbonate secretion mainly in the duodenum and NaCl absorption mainly in the colon. Both SLC26A3 and SLC26A6 were shown in model systems to be functionally and maybe also structurally coupled to CFTR or NHE3 respectively, but these interactions have not been studied in vivo. Furthermore, such interactions may be dynamically regulated if SLC26A3/A6 as well as NHE3 and CFTR are present within the same cell. Fluid secretion and absorption vary in the duodenum and colon several times a day along the fasting/feeding cycle (prandial, post-prandial and interprandial phases), but the corresponding common regulation of the transporters involved – including both their functional and their structural coupling – are not known. We will elucidate regulation of SLC26A3 and SLC26A6 in their interaction with CFTR or NHE3 along the fasting/feeding cycle on the cellular and molecular level. Building on our common expertise and data obtained in the first funding period, we will use human biopsies, a mouse model of fasting/feeding, and human duodenal and colonic organoids, which are differentiated to model crypt or surface cells and are responsive to extracellular signals of the fasting/feeding cycle (Polypeptide YY/Neuropeptide Y, glucose, luminal acid exposure, lysophosphatidic acid). We will also use transfected cells to further characterize and manipulate molecular interactions, including the presence in common multiprotein complexes, the role of PDZ interactions and of lipid rafts. We anticipate to develop a comprehensive picture of how SLC26A3/A6 dependent apical transport processes are regulated along the fasting/feeding cycle in the duodenum and colon.
DFG Programme
Research Units
