Autophagy is an evolutionary conserved catabolic process involved in several physiological and pathological processes such as cancer and neurodegeneration. Autophagy initiation signaling requires both the ULK1 kinase and the BECLIN 1-VPS34 core complex to generate autophagosomes, double-membraned vesicles that transfer cellular contents to lysosomes. In this study, we show that the BECLIN 1-VPS34 complex is tethered to the cytoskeleton through an interaction between the BECLIN 1-interacting protein AMBRA1 and dynein light chains 1/2. When autophagy is induced, ULK1 phosphorylates AMBRA1, releasing the autophagy core complex from dynein. Its subsequent relocalization to the endoplasmic reticulum enables autophagosome nucleation. Therefore, AMBRA1 constitutes a direct regulatory link between ULK1 and BECLIN 1-VPS34, which is required for core complex positioning and activity within the cell. Moreover, our results demonstrate that in addition to a function for microtubules in mediating autophagosome transport, there is a strict and regulatory relationship between cytoskeleton dynamics and autophagosome formation.

DI BARTOLOMEO, S., Corazzari, M., Nazio, F., Oliverio, S., Lisi, G., Antonioli, M., et al. (2010). The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy. THE JOURNAL OF CELL BIOLOGY, 191(1), 155-168 [10.1083/jcb.201002100].

The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy

DI BARTOLOMEO, SABRINA;CORAZZARI, MARCO;Nazio, F;Antonioli, M;Fuoco, C;PIACENTINI, MAURO;CECCONI, FRANCESCO;
2010-10-04

Abstract

Autophagy is an evolutionary conserved catabolic process involved in several physiological and pathological processes such as cancer and neurodegeneration. Autophagy initiation signaling requires both the ULK1 kinase and the BECLIN 1-VPS34 core complex to generate autophagosomes, double-membraned vesicles that transfer cellular contents to lysosomes. In this study, we show that the BECLIN 1-VPS34 complex is tethered to the cytoskeleton through an interaction between the BECLIN 1-interacting protein AMBRA1 and dynein light chains 1/2. When autophagy is induced, ULK1 phosphorylates AMBRA1, releasing the autophagy core complex from dynein. Its subsequent relocalization to the endoplasmic reticulum enables autophagosome nucleation. Therefore, AMBRA1 constitutes a direct regulatory link between ULK1 and BECLIN 1-VPS34, which is required for core complex positioning and activity within the cell. Moreover, our results demonstrate that in addition to a function for microtubules in mediating autophagosome transport, there is a strict and regulatory relationship between cytoskeleton dynamics and autophagosome formation.
4-ott-2010
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/06 - ANATOMIA COMPARATA E CITOLOGIA
English
Con Impact Factor ISI
Dyneins; Protein-Serine-Threonine Kinases; Cells, Cultured; Endoplasmic Reticulum; Autophagy; RNA Interference; Membrane Proteins; Tumor Suppressor Proteins; Down-Regulation; Carrier Proteins; Apoptosis Regulatory Proteins; Humans; GTPase-Activating Proteins; Intracellular Signaling Peptides and Proteins; Signal Transduction; Phosphorylation
DI BARTOLOMEO, S., Corazzari, M., Nazio, F., Oliverio, S., Lisi, G., Antonioli, M., et al. (2010). The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy. THE JOURNAL OF CELL BIOLOGY, 191(1), 155-168 [10.1083/jcb.201002100].
DI BARTOLOMEO, S; Corazzari, M; Nazio, F; Oliverio, S; Lisi, G; Antonioli, M; Pagliarini, V; Matteoni, S; Fuoco, C; Giunta, L; D'Amelio, M; Nardacci, ...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/19333
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