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10.1038/s41467-018-05254-w

http://scihub22266oqcxt.onion/10.1038/s41467-018-05254-w
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C6054611!6054611!30030437
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suck abstract from ncbi


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pmid30030437      Nat+Commun 2018 ; 9 (ä): ä
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  • An autophagy assay reveals the ESCRT-III component CHMP2A as a regulator of phagophore closure #MMPMID30030437
  • Takahashi Y; He H; Tang Z; Hattori T; Liu Y; Young MM; Serfass JM; Chen L; Gebru M; Chen C; Wills CA; Atkinson JM; Chen H; Abraham T; Wang HG
  • Nat Commun 2018[]; 9 (ä): ä PMID30030437show ga
  • The mechanism of phagophore closure remains unclear due to technical limitations in distinguishing unclosed and closed autophagosomal membranes. Here, we report the HaloTag-LC3 autophagosome completion assay that specifically detects phagophores, nascent autophagosomes, and mature autophagic structures. Using this assay, we identify the endosomal sorting complexes required for transport (ESCRT)-III component CHMP2A as a critical regulator of phagophore closure. During autophagy, CHMP2A translocates to the phagophore and regulates the separation of the inner and outer autophagosomal membranes to form double-membrane autophagosomes. Consistently, inhibition of the AAA-ATPase VPS4 activity impairs autophagosome completion. The ESCRT-mediated membrane abscission appears to be a critical step in forming functional autolysosomes by preventing mislocalization of lysosome-associated membrane glycoprotein 1 to the inner autophagosomal membrane. Collectively, our work reveals a function for the ESCRT machinery in the final step of autophagosome formation and provides a useful tool for quantitative analysis of autophagosome biogenesis and maturation.
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