Advertisement

Open Access

TBC1D5 and the AP2 complex regulate ATG9 trafficking and initiation of autophagy

Doris Popovic, Ivan Dikic

Author Affiliations

  1. Doris Popovic1 and
  2. Ivan Dikic*,1
  1. 1Buchmann Institute for Molecular Life Sciences (BMLS) and Institute of Biochemistry II Goethe University School of Medicine, Frankfurt, Germany
  1. *Corresponding author. Tel: +49 69 6301 5964; Fax: +49 69 6301 5577; E‐mail: ivan.dikic{at}biochem2.de

Abstract

The RabGAP protein TBC1D5 controls cellular endomembrane trafficking processes and binds the retromer subunit VPS29 and the ubiquitin‐like protein ATG8 (LC3). Here, we describe that TBC1D5 also associates with ATG9 and the active ULK1 complex during autophagy. Moreover, ATG9 and TBC1D5 interact with clathrin and the AP2 complex. Depletion of TBC1D5 leads to missorting of ATG9 to late endosomes upon activation of autophagy, whereas inhibition of clathrin‐mediated endocytosis or AP2 depletion alters ATG9 trafficking and its association with TBC1D5. Taken together, our data show that TBC1D5 and the AP2 complex are important novel regulators of the rerouting of ATG9‐containing vesicular carriers toward sites of autophagosome formation.

Synopsis

Embedded Image

The membrane remodeling events that occur during autophagosome formation are incompletely understood. This study shows that the RabGAP protein TBC1D5 and the AP2 complex contribute to the correct sorting of ATG9‐containing vesicles during the initiation of autophagy.

  • TBC1D5 and ATG9 interact with the AP2 complex

  • Upon autophagy activation, TBC1D5 dissociates from the retromer complex and associates with ATG9 and active ULK1

  • Functional clathrin‐mediated endocytosis is required for ATG9 trafficking and its interaction with TBC1D5 during autophagy

  • Received September 13, 2013.
  • Revision received February 6, 2014.
  • Accepted February 10, 2014.

Subscribers, please sign in with your username and password.

List of OpenAthens registered sites, including contact details.