TY  - JOUR
A1  - Lamb, Christopher
A1  - Nühlen, Stefanie
A1  - Judith, Delphine
A1  - Frith, David
A1  - Snijders, Ambrosius P.
A1  - Behrends, Christian
A1  - Tooze, Sharon A.
T1  - TBC1D14 regulates autophagy via the TRAPP complex and ATG9 traffic
T2  - The EMBO journal
N2  - 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.
KW  - Autophagy
KW  - Membrane Trafficking
KW  - Rab proteins
KW  - TRAPP
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50804
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-508047
SN  - 1460-2075
SN  - 0261-4189
N1  - © 2015 The Authors. Published under the terms of the CC BY 4.0 license
VL  - 35
IS  - 3
SP  - 281
EP  - 301
PB  - EMBO Press ; Wiley
CY  - Heidelberg ; Hoboken, NJ [u. a.]
ER  -