Department of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
Department of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA
J Cell Sci. 2018 Nov 30;131(23):jcs217638. doi: 10.1242/jcs.217638.
How vesicle trafficking components actively contribute to regulation of paracrine signaling is unclear. We genetically uncovered a requirement for α-soluble NSF attachment protein (α-Snap) in the activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway during egg development. α-Snap, a well-conserved vesicle trafficking regulator, mediates association of N-ethylmaleimide-sensitive factor (NSF) and SNAREs to promote vesicle fusion. Depletion of or the SNARE family member in epithelia blocks polar cells maintenance and prevents specification of motile border cells. Blocking apoptosis rescues polar cell maintenance in -depleted egg chambers, indicating that the lack of border cells in mutants is due to impaired signaling. Genetic experiments implicate α-Snap and NSF in secretion of a STAT-activating cytokine. Live imaging suggests that changes in intracellular Ca are linked to this event. Our data suggest a cell-type specific requirement for particular vesicle trafficking components in regulated exocytosis during development. Given the central role for STAT signaling in immunity, this work may shed light on regulation of cytokine release in humans.
囊泡运输成分如何主动参与旁分泌信号的调节尚不清楚。我们通过遗传学方法发现，α-可溶性 NSF 附着蛋白（α-Snap）在卵子发育过程中 Janus 激酶/信号转导和转录激活因子（JAK/STAT）途径的激活中是必需的。α-Snap 是一种高度保守的囊泡运输调节剂，介导 N-乙基马来酰亚胺敏感因子（NSF）和 SNARE 之间的关联，以促进囊泡融合。上皮细胞中 α-Snap 或 SNARE 家族成员 的耗竭会阻止极性细胞的维持，并阻止运动缘细胞的特化。阻断凋亡可挽救 -耗尽的卵囊中极性细胞的维持，表明突变体中缺乏边缘细胞是由于信号转导受损所致。遗传实验表明 α-Snap 和 NSF 参与了一种 STAT 激活细胞因子的分泌。实时成像表明，细胞内 Ca 水平的变化与此事件有关。我们的数据表明，在发育过程中，特定囊泡运输成分在受调控的胞吐作用中存在细胞类型特异性的需求。鉴于 STAT 信号在免疫中的核心作用，这项工作可能为人类细胞因子释放的调控提供线索。
