TRAPPC11 has been implicated in membrane traffic and lipid-linked oligosaccharide synthesis, and mutations in TRAPPC11 result in neuromuscular and developmental phenotypes. Here, we show that TRAPPC11 has a role upstream of autophagosome formation during macroautophagy. Upon TRAPPC11 depletion, LC3-positive membranes accumulate prior to, and fail to be cleared during, starvation. A proximity biotinylation assay identified ATG2B and its binding partner WIPI4/WDR45 as TRAPPC11 interactors. TRAPPC11 depletion phenocopies that of ATG2 and WIPI4 and recruitment of both proteins to membranes is defective upon reduction of TRAPPC11. We find that a portion of TRAPPC11 and other TRAPP III proteins localize to isolation membranes. Fibroblasts from a patient with TRAPPC11 mutations failed to recruit ATG2B-WIPI4, suggesting that this interaction is physiologically relevant. Since ATG2B-WIPI4 is required for isolation membrane expansion, our study suggests that TRAPPC11 plays a role in this process. We propose a model whereby the TRAPP III complex participates in the formation and expansion of the isolation membrane at several steps.

中文翻译：

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TRAPPC11通过将ATG2B-WIPI4 / WDR45募集到自噬前体膜而在自噬中发挥作用。

TRAPPC11与膜运输和脂质连接的寡糖合成有关，并且TRAPPC11的突变导致神经肌肉和发育表型。在这里，我们显示TRAPPC11在大自噬过程中在自噬小体形成的上游具有作用。在TRAPPC11耗尽后，LC3阳性膜在饥饿之前积累，而在饥饿期间无法清除。邻近生物素化分析确定ATG2B及其结合伴侣WIPI4 / WDR45为TRAPPC11相互作用子。在TRAPPC11还原后，ATG2和WIPI4的TRAPPC11耗竭表型以及两种蛋白质向膜的募集都是有缺陷的。我们发现TRAPPC11和其他TRAPP III蛋白的一部分本地化到隔离膜。来自具有TRAPPC11突变的患者的成纤维细胞未能募集ATG2B-WIPI4，这表明这种相互作用在生理上是相关的。由于ATG2B-WIPI4是隔离膜扩增所必需的，因此我们的研究表明TRAPPC11在此过程中起作用。我们提出了一个模型，其中TRAPP III复合物在几个步骤中参与了隔离膜的形成和扩展。