Functional importance of polymerization and localization of calsequestrin in C-elegans
Functional importance of polymerization and localization of calsequestrin in C-elegans
复制标题
DOI：
10.1242/jcs.001016
复制
发表时间：
2007-05-01
影响因子：
4
通讯作者：
Ahnn, Joohong
中科院分区：
文献类型：
--
作者：
Cho, Jeong Hoon;Ko, Kyung Min;Ahnn, Joohong
钙螯合蛋白（CSQ-1）作为钙供体和钙受体的双重作用使其成为肌浆网（SR）内一种极好的钙缓冲蛋白。我们已经分离和特点的钙螯合蛋白（csq-1）-空突变体秀丽隐杆线虫。令我们惊讶的是，这种突变体csq-1（jh 109）没有表现出严重的肌肉发育或功能缺陷，但，然而，是高度敏感的钙稳态扰动。通过利用可行的无效突变体，我们研究了CSQ-1的结构域，这些结构域对于聚合和细胞定位很重要，并且是其正确缓冲功能所需的。在用各种CSQ-1构建体拯救的转基因动物中，观察到几种突变的钙螯合蛋白的体内聚合和定位模式与结构-功能关系相关。我们的研究结果表明，CSQ-1的聚合是必不可少的，但不足以正确的细胞定位和CSQ-1的功能。此外，首次发现CSQ-1与Ryanodine受体（RyR）直接相互作用，提示CSQ-1在C.确实是由RyR通过物理相互作用调节的。
Dual roles of calsequestrin (CSQ-1) being the Ca2+ donor and Ca2+ acceptor make it an excellent Ca2+- 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 Ca2+ 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.