title: Starvation-induced hyperacetylation of tubulin is required for the stimulation of autophagy by nutrient deprivation.
abstract: The molecular mechanisms underlying microtubule participation in autophagy are not known. In this study, we show that starvation-induced autophagosome formation requires the most dynamic microtubule subset. Upon nutrient deprivation, labile microtubules specifically recruit markers of autophagosome formation like class III-phosphatidylinositol kinase, WIPI-1, the Atg12-Atg5 conjugate, and LC3-I, whereas mature autophagosomes may bind to stable microtubules. We further found that upon nutrient deprivation, tubulin acetylation increases both in labile and stable microtubules and is required to allow autophagy stimulation. Tubulin hyperacetylation on lysine 40 enhances kinesin-1 and JIP-1 recruitment on microtubules and allows JNK phosphorylation and activation. JNK, in turn, triggers the release of Beclin 1 from Bcl-2-Beclin 1 complexes and its recruitment on microtubules where it may initiate autophagosome formation. Finally, although kinesin-1 functions to carry autophagosomes in basal conditions, it is not involved in motoring autophagosomes after nutrient deprivation. Our results show that the dynamics of microtubules and tubulin post-translational modifications play a major role in the regulation of starvation-induced autophagy.
authors.affiliation: Faculté de Pharmacie, University Paris-Sud 11, JE 2493, IFR141, Châtenay-Malabry, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Geeraert
authors.forename: Ameetha
authors.initials: A
authors.lastname: Ratier
authors.forename: Simon G
authors.initials: SG
authors.lastname: Pfisterer
authors.forename: Daniel
authors.initials: D
authors.lastname: Perdiz
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cantaloube
authors.forename: Audrey
authors.initials: A
authors.lastname: Rouault
authors.forename: Sophie
authors.initials: S
authors.lastname: Pattingre
authors.forename: Tassula
authors.initials: T
authors.lastname: Proikas-Cezanne
authors.forename: Patrice
authors.initials: P
authors.lastname: Codogno
authors.forename: Christian
authors.initials: C
authors.lastname: Poüs
mesh_terms: D000107:Acetylation; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry; D001343:Autophagy; D000071186:Beclin-1; D004398:Dyneins / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000737:chemistry; D008239:Lysine / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry*
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C488101:KIF5B protein, human; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014404:Tubulin; D004398:Dyneins; D016547:Kinesins; D008239:Lysine