Phosphorylation of skeletal muscle calsequestrin enhances its Ca2+ binding capacity and promotes its association with junctin

Date

2008

Authors

Beard, Nicole
Wei, Lan
Cheung, Stephanie
Kimura, Takashi
Varsanyi, Magdolna
Dulhunty, Angela

Journal Title

Journal ISSN

Volume Title

Publisher

Elsevier

Abstract

Calcium signaling, intrinsic to skeletal and cardiac muscle function, is critically dependent on the amount of calcium stored within the sarcoplasmic reticulum. Calsequestrin, the main calcium buffer in the sarcoplasmic reticulum, provides a pool of calcium for release through the ryanodine receptor and acts as a luminal calcium sensor for the channel via its interactions with triadin and junctin. We examined the influence of phosphorylation of calsequestrin on its ability to store calcium, to polymerise and to regulate ryanodine receptors by binding to triadin and junctin. Our hypothesis was that these parameters might be altered by phosphorylation of threonine 353, which is located near the calcium and triadin/junctin binding sites. Although phosphorylation increased the calcium binding capacity of calsequestrin nearly 2-fold, it did not alter calsequestrin polymerisation, its binding to triadin or junctin or inhibition of ryanodine receptor activity at 1 mM luminal calcium. Phosphorylation was required for calsequestrin binding to junctin when calcium concentration was low (100 nM), and ryanodine receptors were activated by dephosphorylated calsequestrin when it bound to triadin alone. These novel data shows that phosphorylated calsequestrin is required for high capacity calcium buffering and suggest that ryanodine receptor inhibition by calsequestrin is mediated by junctin.

Description

Keywords

Keywords: calcium ion; calsequestrin; cell protein; junctin; muscle protein; ryanodine receptor; threonine; triadin; animal tissue; article; binding site; calcium binding; calcium homeostasis; calcium signaling; concentration response; controlled study; nonhuman; p Calsequestrin; Junctin; Phosphorylation; Ryanodine receptor; Skeletal muscle; Triadin

Citation

Source

Cell Calcium

Type

Journal article

Book Title

Entity type

Access Statement

License Rights

DOI

10.1016/j.ceca.2008.01.005

Restricted until

2037-12-31