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Starvation andULK1-dependentcycling of mammalianAtg9 between the TGNand endosomes Andrew YoungEdmond Y.W. ChanXiao Wen Hu2006 год

Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes
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Страница публикацииПубликация в OpenAlex
Аннотация: 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.
Год издания: 2006
Авторы: Andrew Young, Edmond Y.W. Chan, Xiao Wen Hu, Robert Köchl, Samuel G. Crawshaw, Stephen High, Dale W. Hailey, Jennifer Lippincott‐Schwartz, Sharon A. Tooze
Издательство: The Company of Biologists
Источник: Journal of Cell Science
Ключевые слова: Autophagy in Disease and Therapy, Cellular transport and secretion, Calcium signaling and nucleotide metabolism
Другие ссылки: Journal of Cell Science (HTML)
PubMed (HTML)