RRC ID 10924
Author Vazquez G, Wedel BJ, Bird GS, Joseph SK, Putney JW.
Title An inositol 1,4,5-trisphosphate receptor-dependent cation entry pathway in DT40 B lymphocytes.
Journal EMBO J.
Abstract We examined the roles of inositol 1,4,5-trisphosphate (IP3) receptors (IP3R) in calcium signaling using DT40 B lymphocytes, and a variant lacking the three IP3R isoforms (IP3R-KO). In wild-type cells, B cell receptor (BCR) stimulation activates a cation entry route that exhibits significantly greater permeability to Ba2+ than does capacitative calcium entry. This cation entry is absent in IP3R-KO cells. Expression of the type-3 IP3R (IP3R-3) in the IP3R-KO cells rescued not only agonist-dependent release of intracellular Ca2+, but also Ba2+ influx following receptor stimulation. Similar results were obtained with an IP3R-3 mutant carrying a conservative point mutation in the selectivity filter region of the channel (D2477E); however, an IP3R-3 mutant in which this same aspartate was replaced by alanine (D2477A) failed to restore either BCR-induced Ca2+ release or receptor-dependent Ba2+ entry. These results suggest that in DT40 B lymphocytes, BCR stimulation activates a novel cation entry across the plasma membrane that depends upon, or is mediated by, fully functional IP3R.
Volume 21(17)
Pages 4531-8
Published 2002-9-2
DOI 10.1093/emboj/cdf467
PMID 12198155
PMC PMC126200
MeSH Amino Acid Substitution Animals B-Lymphocytes / drug effects B-Lymphocytes / metabolism* Barium / metabolism Calcium / metabolism* Calcium Channels / deficiency Calcium Channels / genetics Calcium Channels / physiology* Calcium Signaling / drug effects Calcium Signaling / physiology* Cell Line Chickens Inositol 1,4,5-Trisphosphate Receptors Ion Channel Gating / drug effects Ion Channel Gating / physiology* Mutation, Missense Point Mutation Protein Isoforms / deficiency Protein Isoforms / genetics Protein Isoforms / physiology Rats Receptors, Antigen, B-Cell / physiology Receptors, Cytoplasmic and Nuclear / deficiency Receptors, Cytoplasmic and Nuclear / genetics Receptors, Cytoplasmic and Nuclear / physiology* Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / physiology Thapsigargin / pharmacology Transfection
IF 11.227
Times Cited 44
Human and Animal Cells DT40 (RCB1464) IP3R^(-) DT40 (RCB1467)