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A location, location, location mutation impairs DNM2-mediated release of nascent autophagosomes from recycling endosomes.
Autophagy ( IF 14.6 ) Pub Date : 2020-05-26 , DOI: 10.1080/15548627.2020.1764210
Claudia Puri 1, 2 , David C Rubinsztein 1, 2
Affiliation  

Elucidation of the membranes contributing to autophagosomes has been a critical question in the field, and an area of active research. Recently, we showed that key events in autophagosome formation, from PtdIns3P formation/WIPI2 recruitment to LC3-GABARAP membrane conjugation, occur on the RAB11A-positive compartment (recycling endosomes). This observation raised the question of how the LC3-positive autophagosome precursors detach from the recycling endosome. We recently observed that DNM2 (dynamin 2) mediates this step, and described how the DNM2R465W mutation that causes centronuclear myopathy (CNM) leads to the accumulation of autophagic structures on recycling endosomes, thereby stalling macroautophagy/autophagy. This physiologically important step highlights the importance of understanding release of nascent autophagosomes from the recycling endosomes as part of the autophagy itinerary.



中文翻译:

位置,位置,位置突变会损害DNM2介导的新生自噬体从回收内体的释放。

阐明促成自噬体的膜一直是该领域的一个关键问题,也是一个活跃的研究领域。最近,我们显示自噬体形成中的关键事件,从PtdIns3P形成/ WIPI2募集到LC3-GABARAP膜结合,发生在RAB11A阳性区室(回收内体)上。该观察结果提出了一个问题,即LC3阳性自噬小体前体如何与回收内体分离。我们最近观察到DNM2(动力蛋白2)介导了这一步骤,并描述了DNM2 R465W如何引起中心核肌病(CNM)的突变导致自噬结构在回收内体上的积累,从而使宏观自噬/自噬失速。这个生理学上重要的步骤凸显了理解新生自噬体从回收内体中释放作为自噬行程一部分的重要性。

更新日期:2020-06-30
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