Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes

Andrew R.J. Young, Edmond Y W Chan, Xiao Wen Hu, Robert Köchl, Samuel G Crawshaw, Stephen High, Dale W Hailey, Jennifer Lippincott-Schwartz, Sharon A. Tooze

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Abstract

Autophagy, fundamentally a lysosomal degradation pathway, functions in cells during normal growth and certain pathological conditions, including starvation, to maintain homeostasis. Autophagosomes are formed through a mechanism that is not well understood, despite the identification of many genes required for autophagy. We have studied the mammalian homologue of Atg9p, a multi-spanning transmembrane protein essential in yeast for autophagy, to gain a better understanding of the function of this ubiquitious protein. We show that both the N- and C-termini of mammalian Atg9 (mAtg9) are cytosolic, and predict that mAtg9 spans the membrane six times. We find that mAtg9 is located in the trans-Golgi network and late endosomes and colocalizes with TGN46, the cation-independent mannose-6-phosphate receptor, Rab7 and Rab9. Amino acid starvation or rapamycin treatment, which upregulates autophagy, causes a redistribution of mAtg9 from the TGN to peripheral, endosomal membranes, which are positive for the autophagosomal marker GFP-LC3. siRNA-mediated depletion of the putative mammalian homologue of Atg1p, ULK1, inhibits this starvation-induced redistribution. The redistribution of mAtg9 also requires PI 3-kinase activity, and is reversed after restoration of amino acids. We speculate that starvation-induced autophagy, which requires mAtg9, may rely on an alteration of the steady-state trafficking of mAtg9, in a Atg1-dependent manner.

Original languageEnglish
Pages (from-to)3888-3900
Number of pages13
JournalJournal of Cell Science
Volume119
Issue number18
DOIs
Publication statusPublished - 15 Sep 2006

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Keywords

  • animals
  • endosomes
  • green fluorescent proteins
  • humans
  • intracellular signaling peptides and proteins
  • membrane proteins
  • protein transport
  • protein-serine-threonine kinases
  • rats
  • recombinant fusion proteins
  • rab GTP-binding proteins
  • trans-Golgi Network

Cite this

Young, A. R. J., Chan, E. Y. W., Hu, X. W., Köchl, R., Crawshaw, S. G., High, S., ... Tooze, S. A. (2006). Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. Journal of Cell Science, 119(18), 3888-3900. https://doi.org/10.1242/jcs.03172