RRC ID 45527
Author Allman E, Wang Q, Walker RL, Austen M, Peters MA, Nehrke K.
Title Calcineurin homologous proteins regulate the membrane localization and activity of sodium/proton exchangers in C. elegans.
Journal Am J Physiol Cell Physiol
Abstract Calcineurin B homologous proteins (CHP) are N-myristoylated, EF-hand Ca(2+)-binding proteins that bind to and regulate Na(+)/H(+) exchangers, which occurs through a variety of mechanisms whose relative significance is incompletely understood. Like mammals, Caenorhabditis elegans has three CHP paralogs, but unlike mammals, worms can survive CHP loss-of-function. However, mutants for the CHP ortholog PBO-1 are unfit, and PBO-1 has been shown to be required for proton signaling by the basolateral Na(+)/H(+) exchanger NHX-7 and for proton-coupled intestinal nutrient uptake by the apical Na(+)/H(+) exchanger NHX-2. Here, we have used this genetic model organism to interrogate PBO-1's mechanism of action. Using fluorescent tags to monitor Na(+)/H(+) exchanger trafficking and localization, we found that loss of either PBO-1 binding or activity caused NHX-7 to accumulate in late endosomes/lysosomes. In contrast, NHX-2 was stabilized at the apical membrane by a nonfunctional PBO-1 protein and was only internalized following its complete loss. Additionally, two pbo-1 paralogs were identified, and their expression patterns were analyzed. One of these contributed to the function of the excretory cell, which acts like a kidney in worms, establishing an alternative model for testing the role of this protein in membrane transporter trafficking and regulation. These results lead us to conclude that the role of CHP in Na(+)/H(+) exchanger regulation differs between apical and basolateral transporters. This further emphasizes the importance of proper targeting of Na(+)/H(+) exchangers and the critical role of CHP family proteins in this process.
Volume 310(3)
Pages C233-42
Published 2016-2-1
DOI 10.1152/ajpcell.00291.2015
PII ajpcell.00291.2015
PMID 26561640
MeSH Amino Acid Sequence Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Calcineurin / genetics Calcineurin / metabolism* Cell Membrane / metabolism* Endosomes / metabolism Gene Expression Regulation Lysosomes / metabolism Molecular Sequence Data Mutation Protein Stability Protein Transport Recombinant Fusion Proteins / metabolism Sodium-Hydrogen Exchangers / genetics Sodium-Hydrogen Exchangers / metabolism*
IF 3.485
Times Cited 1
C.elegans tm3716