Starvation and Ulk1-dependent Cycling of Mammalian Atg9 Between the Tgn and Endosomes.
From: Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London, WC2A 3PX, UK.
Journal of cell science
- Publish Date: Sep 2006
- ISSN: 0021-9533
- Volume: 119
- Issue: Pt 18
- Pages: 3888-900
- Medium: Print
- Language: English
- Citation (JAMA): Young Andrew R J, Chan Edmond Y W, Hu Xiao Wen, et al. Starvation and Ulk1-dependent Cycling of Mammalian Atg9 Between the Tgn and Endosomes.. J. Cell. Sci. Sep 2006;119:3888-900
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.
Mesh Headings (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
Check for Full Text / PubMed Unique Identifier (PMID): 16940348
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