Rab GTPase-activating proteins in autophagy: Regulation of endocytic and autophagy pathways by direct binding to human ATG8 modifiers

Doris Popovic, Masato Akutsu, Ivana Novak, J. Wade Harper, Christian Behrends, Ivan Dikic

研究成果: Article査読

131 被引用数 (Scopus)

抄録

Autophagy is an evolutionarily conserved degradation pathway characterized by dynamic rearrangement of membranes that sequester cytoplasm, protein aggregates, organelles, and pathogens for delivery to the vacuole and lysosome, respectively. The ability of autophagosomal membranes to act selectively toward specific cargo is dependent on the small ubiquitin-like modifier ATG8/LC3 and the LC3-interacting region (LIR) present in autophagy receptors. Here, we describe a comprehensive proteinprotein interaction analysis of TBC (Tre2, Bub2, and Cdc16) domain-containing Rab GTPase-activating proteins (GAPs) as potential autophagy adaptors. We identified 14 TBC domain-containing Rab GAPs that bind directly to ATG8 modifiers and that colocalize with LC3-positive autophagy membranes in cells. Intriguingly, one of our screening hits, TBC1D5, contains two LIR motifs. The N-terminal LIR was critical for interaction with the retromer complex and transport of cargo. Direct binding of the retromer component VPS29 to TBC1D5 could be titrated out by LC3, indicating a molecular switch between endosomes and autophagy. Moreover, TBC1D5 could bridge the endosome and autophagosome via its C-terminal LIR motif. During starvationinduced autophagy, TBC1D5 was relocalized from endosomal localization to the LC3-positive autophagosomes. We propose that LC3-interacting Rab GAPs are implicated in the reprogramming of the endocytic trafficking events under starvation-induced autophagy.

本文言語English
ページ(範囲)1733-1744
ページ数12
ジャーナルMolecular and cellular biology
32
9
DOI
出版ステータスPublished - 2012 5月
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 細胞生物学

フィンガープリント

「Rab GTPase-activating proteins in autophagy: Regulation of endocytic and autophagy pathways by direct binding to human ATG8 modifiers」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル