In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 93, No. 24 ( 1996-11-26), p. 13808-13813
Abstract:
A previously uncharacterized 22-kDa Ca 2+ -binding
protein that also binds guanosine nucleotides was characterized, cloned, and analyzed by electrophysiological techniques. The cloned
protein, calexcitin, contains two EF-hands and also has homology with GTP-binding proteins in the ADP ribosylation factor family. In addition
to binding two molecules of Ca 2+ , calexcitin bound GTP and
possessed GTPase activity. Calexcitin is also a high affinity substrate for protein kinase C. Application of calexcitin to the inner surface of
inside-out patches of human fibroblast membranes, in the presence of Ca 2+ and the absence of endogenous
Ca 2+ /calmodulin kinase type II or
protein kinase C activity, reduced the mean open time and mean open probability of 115 ± 6 pS K + channels. Calexcitin
thus appears to directly regulate K + channels. When
microinjected into molluscan neurons or rabbit cerebellar Purkinje cell dendrites, calexcitin was highly effective in enhancing membrane
excitability. Because calexcitin translocates to the cell membrane after phosphorylation, calexcitin could serve as a
Ca 2+ -activated signaling molecule that increases cellular
excitability, which would in turn increase Ca 2+ influx through the membrane. This is also the first known instance of a
GTP-binding protein that binds Ca 2+ .
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.93.24.13808
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1996
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12