The calmodulin regulator protein, PEP-19, sensitizes ATP-induced Ca2+ release.
J Biol Chem
; 288(3): 2040-8, 2013 Jan 18.
Article
em En
| MEDLINE
| ID: mdl-23204517
ABSTRACT
PEP-19 is a small, intrinsically disordered protein that binds to the C-domain of calmodulin (CaM) via an IQ motif and tunes its Ca(2+) binding properties via an acidic sequence. We show here that the acidic sequence of PEP-19 has intrinsic Ca(2+) binding activity, which may modulate Ca(2+) binding to CaM by stabilizing an initial Ca(2+)-CaM complex or by electrostatically steering Ca(2+) to and from CaM. Because PEP-19 is expressed in cells that exhibit highly active Ca(2+) dynamics, we tested the hypothesis that it influences ligand-dependent Ca(2+) release. We show that PEP-19 increases the sensitivity of HeLa cells to ATP-induced Ca(2+) release to greatly increase the percentage of cells responding to sub-saturating doses of ATP and increases the frequency of Ca(2+) oscillations. Mutations in the acidic sequence of PEP-19 that inhibit or prevent it from modulating Ca(2+) binding to CaM greatly inhibit its effect on ATP-induced Ca(2+) release. Thus, this cellular effect of PEP-19 does not depend simply on binding to CaM via the IQ motif but requires its acidic metal binding domain. Tuning the activities of Ca(2+) mobilization pathways places PEP-19 at the top of CaM signaling cascades, with great potential to exert broad effects on downstream CaM targets, thus expanding the biological significance of this small regulator of CaM signaling.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Calmodulina
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Cálcio
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Sinalização do Cálcio
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Proteínas do Tecido Nervoso
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article