Two Independent Pathways Within Selective Autophagy Converge to Activate Atg1 Kinase at the Vacuole

Mol Cell. 2016 Oct 20;64(2):221-235. doi: 10.1016/j.molcel.2016.09.008.

Abstract

Autophagy is a potent cellular degradation pathway, and its activation needs to be tightly controlled. Cargo receptors mediate selectivity during autophagy by bringing cargo to the scaffold protein Atg11 and, in turn, to the autophagic machinery, including the central autophagy kinase Atg1. Here we show how selective autophagy is tightly regulated in space and time to prevent aberrant Atg1 kinase activation and autophagy induction. We established an induced bypass approach (iPass) that combines genetic deletion with chemically induced dimerization to evaluate the roles of Atg13 and cargo receptors in Atg1 kinase activation and selective autophagy progression. We show that Atg1 activation does not require cargo receptors, cargo-bound Atg11, or Atg13 per se. Rather, these proteins function in two independent pathways that converge to activate Atg1 at the vacuole. This pathway architecture underlies the spatiotemporal control of Atg1 kinase activity, thereby preventing inappropriate autophagosome formation.

Keywords: Atg1-ULK1 kinase; Atg11; Atg13; Atg19; Atg36; Cvt pathway; autophagy; iPass; pexophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Aminopeptidases / genetics
  • Aminopeptidases / metabolism
  • Autophagy / genetics*
  • Autophagy-Related Proteins / genetics*
  • Autophagy-Related Proteins / metabolism
  • Gene Expression Regulation, Fungal*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Phagosomes / metabolism
  • Protein Kinases / genetics*
  • Protein Kinases / metabolism
  • Protein Multimerization
  • Protein Transport
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Transduction
  • Vacuoles / metabolism
  • Vesicular Transport Proteins / genetics*
  • Vesicular Transport Proteins / metabolism

Substances

  • ATG13 protein, S cerevisiae
  • ATG19 protein, S cerevisiae
  • Adaptor Proteins, Signal Transducing
  • Atg11 protein, S cerevisiae
  • Autophagy-Related Proteins
  • Receptors, Cell Surface
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Vesicular Transport Proteins
  • Green Fluorescent Proteins
  • Protein Kinases
  • ATG1 protein, S cerevisiae
  • Aminopeptidases
  • APE1 protein, S cerevisiae