TBC1D14 regulates autophagy via the TRAPP complex and ATG9 traffic

  • Macroautophagy requires membrane trafficking and remodelling to form the autophagosome and deliver its contents to lysosomes for degradation. We have previously identified the TBC domain‐containing protein, TBC1D14, as a negative regulator of autophagy that controls delivery of membranes from RAB11‐positive recycling endosomes to forming autophagosomes. In this study, we identify the TRAPP complex, a multi‐subunit tethering complex and GEF for RAB1, as an interactor of TBC1D14. TBC1D14 binds to the TRAPP complex via an N‐terminal 103 amino acid region, and overexpression of this region inhibits both autophagy and secretory traffic. TRAPPC8, the mammalian orthologue of a yeast autophagy‐specific TRAPP subunit, forms part of a mammalian TRAPPIII‐like complex and both this complex and TBC1D14 are needed for RAB1 activation. TRAPPC8 modulates autophagy and secretory trafficking and is required for TBC1D14 to bind TRAPPIII. Importantly, TBC1D14 and TRAPPIII regulate ATG9 trafficking independently of ULK1. We propose a model whereby TBC1D14 and TRAPPIII regulate a constitutive trafficking step from peripheral recycling endosomes to the early Golgi, maintaining the cycling pool of ATG9 required for initiation of autophagy.
Author:Christopher Lamb, Stefanie Nühlen, Delphine Judith, David Frith, Ambrosius P. Snijders, Christian Behrends, Sharon A. Tooze
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/26711178
Parent Title (English):The EMBO journal
Publisher:EMBO Press ; Wiley
Place of publication:Heidelberg ; Hoboken, NJ [u. a.]
Document Type:Article
Year of Completion:2015
Date of first Publication:2015/12/28
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/07/29
Tag:Autophagy; Membrane Trafficking; Rab proteins; TRAPP
Page Number:21
First Page:281
Last Page:301
© 2015 The Authors. Published under the terms of the CC BY 4.0 license
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0