生物
细胞生物学
内体
肌球蛋白
免疫突触
肌动蛋白细胞骨架
细胞迁移
肌动蛋白
小型GTPase
细胞骨架
内吞作用
细胞
信号转导
免疫系统
T细胞
免疫学
生物化学
T细胞受体
细胞内
作者
Katharina Vestre,Irene Persiconi,Marita Borg Distefano,Nadia Mensali,Noemi Antonella Guadagno,Marine Bretou,Sébastien Wälchli,Catharina Arnold-Schrauf,Oddmund Bakke,Marc Dalod,Ana-María Lennon-Duménil,Cinzia Progida
摘要
ABSTRACT Lysosomal signaling facilitates the migration of immune cells by releasing Ca2+ to activate the actin-based motor myosin II at the cell rear. However, how the actomyosin cytoskeleton physically associates to lysosomes is unknown. We have previously identified myosin II as a direct interactor of Rab7b, a small GTPase that mediates the transport from late endosomes/lysosomes to the trans-Golgi network (TGN). Here, we show that Rab7b regulates the migration of dendritic cells (DCs) in one- and three-dimensional environments. DCs are immune sentinels that transport antigens from peripheral tissues to lymph nodes to activate T lymphocytes and initiate adaptive immune responses. We found that the lack of Rab7b reduces myosin II light chain phosphorylation and the activation of the transcription factor EB (TFEB), which controls lysosomal signaling and is required for fast DC migration. Furthermore, we demonstrate that Rab7b interacts with the lysosomal Ca2+ channel TRPML1 (also known as MCOLN1), enabling the local activation of myosin II at the cell rear. Taken together, our findings identify Rab7b as the missing physical link between lysosomes and the actomyosin cytoskeleton, allowing control of immune cell migration through lysosomal signaling. This article has an associated First Person interview with the first author of the paper.
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