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

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.
Santosh Chauhan 1,  Suresh Kumar 1,  Ashish Jain 2,  Marisa Ponpuak 3,  Michal H Mudd 1,  Tomonori Kimura 1,  Seong Won Choi 1,  Ryan Peters 1,  Michael Mandell 1,  Jack-Ansgar Bruun 2,  Terje Johansen 4,  Vojo Deretic 5
Affiliations

Affiliations

  • 1 Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, Northeast, Albuquerque, NM 87131, USA.
  • 2 Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø - The Arctic University of Norway, 9037 Tromsø, Norway.
  • 3 Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, Northeast, Albuquerque, NM 87131, USA; Department of Microbiology, Faculty of Science, Mahidol University, 272 Rama VI, Rachathewi, Bangkok 10400, Thailand.
  • 4 Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø - The Arctic University of Norway, 9037 Tromsø, Norway. Electronic address: terje.johansen@uit.no.
  • 5 Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, Northeast, Albuquerque, NM 87131, USA. Electronic address: vderetic@salud.unm.edu.
PMID: 27693506 DOI: 10.1016/j.devcel.2016.08.003
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.

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