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Role of an extracellular loop in determining the stoichiometry of Na + –HCO 3 − cotransporters
Author(s) -
Chen LiMing,
Liu Ying,
Boron Walter F.
Publication year - 2011
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2010.198713
Subject(s) - cotransporter , extracellular , chemistry , stoichiometry , intracellular ph , intracellular , biophysics , biochemistry , sodium , biology , organic chemistry
Non‐technical summary The Na + –HCO 3 − cotransporters NBCe1 and NBCn1 play critical roles in the regulation of intracellular pH and in acid–base movement across epithelial barriers such as the kidney. NBCe1 appears to carry 1 Na + for every 2 or 3 HCO 3 − and thus is electrogenic (carries electrical current) and NBCn1 appears to carry 1 Na + for every 1 HCO 3 − and thus is electroneutral (carries no electrical current). We systematically substituted homologous pieces of NBCn1 into NBCe1 and made the surprising observation that a putative extracellular loop (previously thought to be an unstructured segment of protein that dangles in the extracellular fluid) plays a key role in determining the stoichiometry of NBCe1 and NBCn1. We found that replacing just the fourth extracellular loop of NBCe1 with that of NBCn1 fully eliminates the electrogenicity, and that the opposite substitution converts an electroneutral chimera into one capable of electrogenic transport.