The Rho-GEF PIX-1 directs assembly or stability of lateral attachment structures between muscle cells.

The Rho-GEF PIX-1 directs assembly or stability of lateral attachment structures between muscle cells.
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DOI:
10.1038/s41467-020-18852-4
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发表时间:
2020-10-06
影响因子:
16.6
通讯作者:
Benian GM
Benian GM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Moody JC;Qadota H;Reedy AR;Okafor CD;Shanmugan N;Matsunaga Y;Christian CJ;Ortlund EA;Benian GM

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PIX 蛋白是激活 Rac 和 Cdc42 的鸟嘌呤核苷酸交换因子 (GEF),已知在各种细胞类型中具有多种功能。在这里,我们证明 PIX 蛋白在肌肉中具有重要功能。通过对秀丽隐杆线虫的遗传筛选,我们发现 pix-1 是肌肉细胞边界处整合素粘附复合物 (IAC) 组装所必需的,也是动物运动所必需的。 pix-1 无效突变体的肌肉中激活的 Rac 水平降低。 PIX-1 定位于肌细胞边界、M 线和致密体处的 IAC。 PIX 信号通路已知步骤中编码蛋白质的基因突变显示出肌肉细胞边界的缺陷。 RacGEF 结构域中高度保守残基的错义突变导致 PIX-1 蛋白水平正常,但肌肉中激活的 Rac 水平降低,以及肌肉细胞边界处的 IAC 异常。 PIX 蛋白可激活小型 GTPases Rac 和 Cdc42,已知在多种细胞类型中具有多种功能。通过对秀丽隐杆线虫进行遗传筛选,作者发现 PIX-1 是肌肉细胞之间整合素粘附复合物的组装或稳定性所必需的。
PIX proteins are guanine nucleotide exchange factors (GEFs) that activate Rac and Cdc42, and are known to have numerous functions in various cell types. Here, we show that a PIX protein has an important function in muscle. From a genetic screen in C. elegans, we found that pix-1 is required for the assembly of integrin adhesion complexes (IACs) at borders between muscle cells, and is required for locomotion of the animal. A pix-1 null mutant has a reduced level of activated Rac in muscle. PIX-1 localizes to IACs at muscle cell boundaries, M-lines and dense bodies. Mutations in genes encoding proteins at known steps of the PIX signaling pathway show defects at muscle cell boundaries. A missense mutation in a highly conserved residue in the RacGEF domain results in normal levels of PIX-1 protein, but a reduced level of activated Rac in muscle, and abnormal IACs at muscle cell boundaries. PIX proteins activate the small GTPases Rac and Cdc42, and are known to have numerous functions in a variety of cell types. Using a genetic screen in C. elegans, the authors find that PIX-1 is required for the assembly or stability of integrin adhesion complexes between muscle cells.
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