Conserved Atg8 recognition sites mediate Atg4 association with autophagosomal membranes and Atg8 deconjugation

Susana Abreu, Franziska Kriegenburg, Rubén Gómez-Sánchez, Muriel Mari, Jana Sanchez-Wandelmer, Mads Skytte Rasmussen, Rodrigo Soares Guimaraes, Bettina Zens, Martina Schuschnig, Ralph Hardenberg, Matthias Peter, Terje Johansen, Claudine Kraft, Sascha Martens, Fulvio Reggiori*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

46 Citaten (Scopus)

Samenvatting

Deconjugation of the Atg8/LC3 protein family members from phosphatidylethanolamine (PE) by Atg4 proteases is essential for autophagy progression, but how this event is regulated remains to be understood. Here, we show that yeast Atg4 is recruited onto autophagosomal membranes by direct binding to Atg8 via two evolutionarily conserved Atg8 recognition sites, a classical LC3-interacting region (LIR) at the C-terminus of the protein and a novel motif at the N-terminus. Although both sites are important for Atg4-Atg8 interaction in vivo, only the new N-terminal motif, close to the catalytic center, plays a key role in Atg4 recruitment to autophagosomal membranes and specific Atg8 deconjugation. We thus propose a model where Atg4 activity on autophagosomal membranes depends on the cooperative action of at least two sites within Atg4, in which one functions as a constitutive Atg8 binding module, while the other has a preference toward PE-bound Atg8.

Originele taal-2English
Pagina's (van-tot)765-780
Aantal pagina's16
TijdschriftEmbo Reports
Volume18
Nummer van het tijdschrift5
DOI's
StatusPublished - mei-2017

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