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

Vittoria Pagliarini, Sabrina Di Bartolomeo, Marco Corazzari, Francesca Nazio, Serafina Oliverio, Gaia Lisi, Manuela Antonioli, Silvia Matteoni, Claudia Fuoco, Luigi Giunta, Marcello D'Amelio, Roberta Nardacci, Alessandra Romagnoli, Mauro Piacentini, Francesco Cecconi, Gian Maria Fimia

Risultato della ricerca: Contributo in rivistaArticolo in rivista

318 Citazioni (Scopus)

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. © 2010 Di Bartolomeo et al.
Lingua originaleEnglish
pagine (da-a)155-168
Numero di pagine14
RivistaTHE JOURNAL OF CELL BIOLOGY
Volume191
DOI
Stato di pubblicazionePubblicato - 2010

Keywords

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Autophagy
  • Autophagy-Related Protein-1 Homolog
  • Beclin-1
  • Carrier Proteins
  • Cells, Cultured
  • Down-Regulation
  • Dyneins
  • Endoplasmic Reticulum
  • GTPase-Activating Proteins
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Phosphorylation
  • Protein-Serine-Threonine Kinases
  • RNA Interference
  • Signal Transduction
  • Tumor Suppressor Proteins

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