Title : Starvation and
ULK1-dependent cycling of mammalian
Atg9 between the TGN and endosomes
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
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*Output_Site_Fusion* (sent_index,
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