Control of autophagy initiation by phosphoinositide 3-phosphatase jumpy
The majority of studies on autophagy, a cytoplasmic homeostatis pathway of broad biological and medical significance, have been hitherto focused on the phosphatidylinositol 3‐kinases as the regulators of autophagy. Here, we addressed the reverse process driven by phosphoinositide phosphatases and un...
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Published in | The EMBO journal Vol. 28; no. 15; pp. 2244 - 2258 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Chichester, UK
John Wiley & Sons, Ltd
05.08.2009
Blackwell Publishing Ltd EMBO Press Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | The majority of studies on autophagy, a cytoplasmic homeostatis pathway of broad biological and medical significance, have been hitherto focused on the phosphatidylinositol 3‐kinases as the regulators of autophagy. Here, we addressed the reverse process driven by phosphoinositide phosphatases and uncovered a key negative regulatory role in autophagy of a phosphatidylinositol 3‐phosphate (PI3P) phosphatase Jumpy (MTMR14). Jumpy associated with autophagic isolation membranes and early autophagosomes, defined by the key factor Atg16 necessary for proper localization and development of autophagic organelles. Jumpy orchestrated orderly succession of Atg factors by controlling recruitment to autophagic membranes of the sole mammalian Atg factor that interacts with PI3P, WIPI‐1 (Atg18), and by affecting the distribution of Atg9 and LC3, the two Atg factors controlling organization and growth of autophagic membranes. A catalytically inactive Jumpy mutant, R336Q, found in congenital disease centronuclear myopathy, lost the ability to negatively regulate autophagy. This work reports for the first time that initiation of autophagy is controlled not only by the forward reaction of generating PI3P through a lipid kinase but that its levels are controlled by a specific PI3P phosphatase, which when defective can lead to human disease. |
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Bibliography: | ark:/67375/WNG-51WW7F39-G ArticleID:EMBJ2009159 istex:54D6E446AAB285807A77001C0F202B0E8D5E7BBF Supplementary MaterialsSupplementary Movie S1Review Process File PMCID: PMC2726690 |
ISSN: | 0261-4189 1460-2075 |
DOI: | 10.1038/emboj.2009.159 |