CHMP5 is essential for late endosome function and down-regulation of receptor signaling during mouse embryogenesis.
CHMP5 is essential for late endosome function and down-regulation of receptor signaling during mouse embryogenesis.
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DOI：
10.1083/jcb.200509041
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发表时间：
2006-03-27
影响因子：
7.8
通讯作者：
Ghosh, Sankar
中科院分区：
文献类型：
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作者：
Shim, Jae-Hyuck;Xiao, Changchun;Hayden, Matthew S;Lee, Ki-Young;Trombetta, E Sergio;Pypaert, Marc;Nara, Atsuki;Yoshimori, Tamotsu;Wilm, Bettina;Erdjument-Bromage, Hediye;Tempst, Paul;Hogan, Brigid L M;Mellman, Ira;Ghosh, Sankar
带电 MVB 蛋白 5 (CHMP5) 是一种卷曲螺旋蛋白，与酵母 Vps60/Mos10 基因和其他 ESCRT-III 复合体成员同源，但其在酵母或哺乳动物细胞中的确切功能尚不清楚。我们删除了小鼠的 CHMP5 基因，导致早期胚胎致死的表型，反映了晚期内体功能缺陷和信号转导失调。 Chmp5 -/− 细胞表现出扩大的晚期内体区室，其中含有丰富的内部囊泡，表达晚期内体和溶酶体所特有的蛋白质。这与酵母中的 ESCRT-III 突变体形成鲜明对比，后者在多泡体 (MVB) 形成方面存在缺陷。 Chmp5 -/− 细胞的降解能力降低，来自多种途径的未消化蛋白质在扩大的 MVB 中积累，无法将其货物运输到溶酶体。因此，CHMP5 调节 MVB 形成下游的晚期内体功能，CHMP5 的缺失通过抑制激活受体的溶酶体降解来增强信号转导。
Charged MVB protein 5 (CHMP5) is a coiled coil protein homologous to the yeast Vps60/Mos10 gene and other ESCRT-III complex members, although its precise function in either yeast or mammalian cells is unknown. We deleted the CHMP5 gene in mice, resulting in a phenotype of early embryonic lethality, reflecting defective late endosome function and dysregulation of signal transduction. Chmp5 −/− cells exhibit enlarged late endosomal compartments that contain abundant internal vesicles expressing proteins that are characteristic of late endosomes and lysosomes. This is in contrast to ESCRT-III mutants in yeast, which are defective in multivesicular body (MVB) formation. The degradative capacity of Chmp5 −/− cells was reduced, and undigested proteins from multiple pathways accumulated in enlarged MVBs that failed to traffic their cargo to lysosomes. Therefore, CHMP5 regulates late endosome function downstream of MVB formation, and the loss of CHMP5 enhances signal transduction by inhibiting lysosomal degradation of activated receptors.