The rod-shaped ATG2A-WIPI4 complex tethers membranes in vitro.
The rod-shaped ATG2A-WIPI4 complex tethers membranes in vitro.
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DOI：
10.1177/2515256418819936
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发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Lander, Gabriel C
中科院分区：
文献类型：
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作者：
Otomo, Takanori;Chowdhury, Saikat;Lander, Gabriel C
自噬体前体膜，称为“隔离膜”或“吞噬细胞”，出现在ER的一个富含PI 3 P的瞬时亚结构域附近，称为“omegasome”，随后扩展以吞噬细胞质内容物。揭示吞噬细胞生物发生期间在omegasome附近发生的分子事件对于了解自噬途径这一关键步骤所涉及的机制至关重要。我们最近的特点是ATG 2A-WIPI 4复合物，本地化的omegasome的因素之一，并在介导吞噬细胞扩张发挥关键作用。我们的结构和生物化学研究表明，ATG 2A是一个杆状蛋白，在每个末端具有膜相互作用的特性，赋予ATG 2A膜束缚能力。PI 3 P结合蛋白WIPI 4在ATG 2A尖端之一处的缔合使得ATG 2A-WIPI 4复合物能够特异性地将含PI 3 P的膜系到不含PI 3 P的膜。我们提出了模型的ATG 2A-WIPI 4复合物介导的omegasome和周围的膜，包括吞噬细胞边缘，ER，ATG 9囊泡，和COPII囊泡之间的膜协会。
The autophagosome precursor membrane, termed the "isolation membrane" or "phagophore," emerges adjacent to a PI3P-enriched transient subdomain of the ER called the "omegasome," thereafter expanding to engulf cytoplasmic content. Uncovering the molecular events that occur in the vicinity of the omegasome during phagophore biogenesis is imperative for understanding the mechanisms involved in this critical step of the autophagy pathway. We recently characterized the ATG2A-WIPI4 complex, one of the factors that localize to the omegasome and play a critical role in mediating phagophore expansion. Our structural and biochemical studies revealed that ATG2A is a rod-shaped protein with membrane-interacting properties at each end, endowing ATG2A with membrane-tethering capability. Association of the PI3P-binding protein WIPI4 at one of the ATG2A tips enables the ATG2A-WIPI4 complex to specifically tether PI3P-containing membranes to non-PI3P-containing membranes. We proposed models for the ATG2A-WIPI4 complex-mediated membrane associations between the omegasome and surrounding membranes, including the phagophore edge, the ER, ATG9 vesicles, and COPII vesicles.