Functional importance of polymerization and localization of calsequestrin in C-elegans

Abstract

Dual roles of calsequestrin (CSQ-1) being the Ca(2+) donor and Ca(2+) acceptor make it an excellent Ca(2+)- buffering protein within the sarcoplasmic reticulum (SR). We have isolated and characterized a calsequestrin (csq-1)-null mutant in Caenorhabditis elegans. To our surprise, this mutant csq-1(jh109) showed no gross defects in muscle development or function but, however, is highly sensitive to perturbation of Ca(2+) homeostasis. By taking advantage of the viable null mutant, we investigated the domains of CSQ-1 that are important for polymerization and cellular localization, and required for its correct buffering functions. In transgenic animals rescued with various CSQ-1 constructs, the in vivo patterns of polymerization and localization of several mutated calsequestrins were observed to correlate with the structure-function relationship. Our results suggest that polymerization of CSQ-1 is essential but not sufficient for correct cellular localization and function of CSQ-1. In addition, direct interaction between CSQ-1 and the ryanodine receptor (RyR) was found for the first time, suggesting that the cellular localization of CSQ-1 in C. elegans is indeed modulated by RyR through a physical interaction.