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TBC 1D14 regulates autophagy via the TRAPP complex and ATG 9 traffic
Author(s) -
Lamb Christopher A,
Nühlen Stefanie,
Judith Delphine,
Frith David,
Snijders Ambrosius P,
Behrends Christian,
Tooze Sharon A
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201592695
Subject(s) - autophagy , microbiology and biotechnology , endosome , rab , protein subunit , golgi apparatus , autophagosome , transport protein , chemistry , biology , endoplasmic reticulum , gtpase , biochemistry , intracellular , gene , apoptosis
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, TBC 1D14, as a negative regulator of autophagy that controls delivery of membranes from RAB 11‐positive recycling endosomes to forming autophagosomes. In this study, we identify the TRAPP complex, a multi‐subunit tethering complex and GEF for RAB 1, as an interactor of TBC 1D14. TBC 1D14 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, TBC 1D14 and TRAPPIII regulate ATG 9 trafficking independently of ULK 1. We propose a model whereby TBC 1D14 and TRAPPIII regulate a constitutive trafficking step from peripheral recycling endosomes to the early Golgi, maintaining the cycling pool of ATG 9 required for initiation of autophagy.