Septins are involved at the early stages of macroautophagy in S. cerevisiae
Septins are involved at the early stages of macroautophagy in S. cerevisiae
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DOI：
10.1242/jcs.209098
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发表时间：
2018-02-01
影响因子：
4
通讯作者：
Manjithaya, Ravi
中科院分区：
文献类型：
--
作者：
Barve, Gaurav;Sridhar, Shreyas;Manjithaya, Ravi
自噬是一种保守的细胞降解途径，其中称为自噬体的双膜囊泡捕获长寿命蛋白质以及受损或多余的细胞器，并将它们递送至溶酶体进行降解。 Septin 是保守的 GTP 结合蛋白，参与许多细胞过程，包括细胞内细菌的吞噬作用和自噬，但在一般自噬中的作用尚不清楚。在出芽酵母中，脓蛋白聚合成胞质分裂所需的环状细丝阵列。在无偏见的遗传筛选和随后的靶向分析中，我们发现 septin 突变体存在自噬缺陷。自噬诱导后，预组装的脓毒蛋白复合物重新定位到自噬体前结构 (PAS)，并在 PAS 处形成非典型的脓毒蛋白环。 Septin 还与自噬体共定位，在自噬体中它们与自噬蛋白 Atg8 和 Atg9 发生物理相互作用。当septin突变细胞中的自噬体降解被阻断时，自噬结构的积累就会减少，并且在自噬体生物发生的早期阶段有缺陷的自噬突变体（atg1 Delta）表现出septin定位到PAS的减少。我们的研究结果支持脓毒蛋白在芽殖酵母自噬的早期阶段以及自噬体形成过程中的作用。
Autophagy is a conserved cellular degradation pathway wherein double-membrane vesicles called autophagosomes capture long-lived proteins, and damaged or superfluous organelles, and deliver them to the lysosome for degradation. Septins are conserved GTP-binding proteins involved in many cellular processes, including phagocytosis and the autophagy of intracellular bacteria, but no role in general autophagy was known. In budding yeast, septins polymerize into ringshaped arrays of filaments required for cytokinesis. In an unbiased genetic screen and in subsequent targeted analysis, we found autophagy defects in septin mutants. Upon autophagy induction, pre-assembled septin complexes relocalized to the preautophagosomal structure (PAS) where they formed non-canonical septin rings at PAS. Septins also colocalized with autophagosomes, where they physically interacted with the autophagy proteins Atg8 and Atg9. When autophagosome degradation was blocked in septinmutant cells, fewer autophagic structures accumulated, and an autophagy mutant defective in early stages of autophagosome biogenesis (atg1 Delta), displayed decreased septin localization to the PAS. Our findings support a role for septins in the early stages of budding yeast autophagy, during autophagosome formation.