TRIMs and Galectins Globally Cooperate and TRIM16 and Galectin-3 Co-direct Autophagy in Endomembrane Damage Homeostasis

Dev Cell. 2016 Oct 10;39(1):13-27. doi: 10.1016/j.devcel.2016.08.003. Epub 2016 Sep 29.

Abstract

Selective autophagy performs an array of tasks to maintain intracellular homeostasis, sterility, and organellar and cellular functionality. The fidelity of these processes depends on precise target recognition and limited activation of the autophagy apparatus in a localized fashion. Here we describe cooperation in such processes between the TRIM family and Galectin family of proteins. TRIMs, which are E3 ubiquitin ligases, displayed propensity to associate with Galectins. One specific TRIM, TRIM16, interacted with Galectin-3 in a ULK1-dependent manner. TRIM16, through integration of Galectin- and ubiquitin-based processes, coordinated recognition of membrane damage with mobilization of the core autophagy regulators ATG16L1, ULK1, and Beclin 1 in response to damaged endomembranes. TRIM16 affected mTOR, interacted with TFEB, and influenced TFEB's nuclear translocation. The cooperation between TRIM16 and Galectin-3 in targeting and activation of selective autophagy protects cells from lysosomal damage and Mycobacterium tuberculosis invasion.

MeSH terms

  • Animals
  • Autophagy*
  • Autophagy-Related Protein-1 Homolog / metabolism
  • Autophagy-Related Proteins / metabolism
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Beclin-1 / metabolism
  • Calcineurin / metabolism
  • Cytoprotection
  • DNA-Binding Proteins / metabolism*
  • Galectin 3 / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Homeostasis*
  • Humans
  • Intracellular Membranes / metabolism*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lysosomes / metabolism
  • Lysosomes / pathology
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Multiprotein Complexes / metabolism
  • Mycobacterium tuberculosis / physiology
  • Phosphorylation
  • Protein Binding
  • Protein Stability
  • RAW 264.7 Cells
  • TOR Serine-Threonine Kinases / metabolism
  • Transcription Factors / metabolism*
  • Ubiquitin / metabolism
  • Ubiquitination

Substances

  • ATG16L1 protein, human
  • Autophagy-Related Proteins
  • BECN1 protein, human
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Beclin-1
  • DNA-Binding Proteins
  • Galectin 3
  • Intracellular Signaling Peptides and Proteins
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins
  • Multiprotein Complexes
  • TFEB protein, human
  • Transcription Factors
  • Ubiquitin
  • TRIM16 protein, human
  • TOR Serine-Threonine Kinases
  • Autophagy-Related Protein-1 Homolog
  • ULK1 protein, human
  • Calcineurin