Synaptotagmin-mediated vesicle fusion regulates cell migration.
Synaptotagmin-mediated vesicle fusion regulates cell migration.
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趋化因子和其他趋化因子指导白细胞迁移，对免疫和炎症反应的发展和传递至关重要。为了探究趋化剂引导迁移的分子机制，我们进行了rna介导的干扰筛选，确定了钙敏感囊泡融合蛋白synaptotagmin家族的几个成员作为细胞迁移的介质：SYT7和SYTL5是趋化性的正调节因子，而SYT2是趋化性的负调节因子。syt7缺陷白细胞在体外和体内痛风模型中表现出较少的迁移。趋化剂诱导的钙依赖性溶酶体融合在syt7缺陷中性粒细胞中受损。在趋化因子梯度中，syt7缺陷淋巴细胞在其尾足中积累溶酶体，并损害尾足释放。我们的数据确定了趋化性所需的分子途径，将趋化剂诱导的钙通量与胞吐和尾足释放联系起来。
Chemokines and other chemoattractants direct leukocyte migration and are essential for the development and delivery of immune and inflammatory responses. To probe the molecular mechanisms that underlie chemoattractant-guided migration, we did an RNA-mediated interference screen that identified several members of the synaptotagmin family of calcium-sensing vesicle-fusion proteins as mediators of cell migration: SYT7 and SYTL5 were positive regulators of chemotaxis, whereas SYT2 was a negative regulator of chemotaxis. SYT7-deficient leukocytes showed less migration in vitro and in a gout model in vivo. Chemoattractant-induced calcium-dependent lysosomal fusion was impaired in SYT7-deficient neutrophils. In a chemokine gradient, SYT7-deficient lymphocytes accumulated lysosomes in their uropods and had impaired uropod release. Our data identify a molecular pathway required for chemotaxis that links chemoattractant-induced calcium flux to exocytosis and uropod release.