The Nesprin-1/-2 ortholog ANC-1 regulates organelle positioning in C. elegans independently from its KASH or actin-binding domains.
The Nesprin-1/-2 ortholog ANC-1 regulates organelle positioning in C. elegans independently from its KASH or actin-binding domains.
复制标题
Nesprin-1/-2直系同源物ANC-1调节C. elegans独立于其KASH或肌动蛋白结合结构域。
DOI：
10.7554/elife.61069
复制
发表时间：
2021-04-16
期刊：
影响因子：
7.7
通讯作者：
Starr DA
中科院分区：
文献类型：
--
作者：
Hao H;Kalra S;Jameson LE;Guerrero LA;Cain NE;Bolivar J;Starr DA
外核膜中的KASH蛋白质包含将核连接到细胞骨架的核骨架和细胞骨架（LINC）复合物的接头的细胞质半部分。秀丽隐杆线虫ANC-1是Nesprin-1/2的直系同源物，在长血影蛋白样区域的两端含有肌动蛋白结合和KASH结构域。KASH或钙调蛋白同源（CH）结构域的缺失不会完全破坏核定位，表明KASH或CH结构域都不是必需的。ANC-1血影蛋白样区域的缺失导致显著缺陷，但仅概括了与跨膜（TM）跨度中的突变相结合的无效表型。在anc-1突变体中，内质网ER、线粒体和脂滴未被锚定，在整个细胞质中移动。本文提供的数据支持细胞质完整性模型，其中ANC-1定位于ER膜并延伸到细胞质中以将细胞核、ER、线粒体和其他细胞器定位在适当位置。
KASH proteins in the outer nuclear membrane comprise the cytoplasmic half of linker of nucleoskeleton and cytoskeleton (LINC) complexes that connect nuclei to the cytoskeleton. Caenorhabditis elegans ANC-1, an ortholog of Nesprin-1/2, contains actin-binding and KASH domains at opposite ends of a long spectrin-like region. Deletion of either the KASH or calponin homology (CH) domains does not completely disrupt nuclear positioning, suggesting neither KASH nor CH domains are essential. Deletions in the spectrin-like region of ANC-1 led to significant defects, but only recapitulated the null phenotype in combination with mutations in the transmembrane (TM) span. In anc-1 mutants, the endoplasmic reticulum ER, mitochondria, and lipid droplets were unanchored, moving throughout the cytoplasm. The data presented here support a cytoplasmic integrity model where ANC-1 localizes to the ER membrane and extends into the cytoplasm to position nuclei, ER, mitochondria, and other organelles in place.