Galectin-3 Coordinates a Cellular System for Lysosomal Repair and Removal.

FULLTEXT
Published:
12.10.2019
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Last Revised:
03.17.2020
PMID:
31813797
Developmental cell
Journal Article
Authors:
Autophagy Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA.
Autophagy Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA.
Autophagy Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA.
Autophagy Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA.
Autophagy Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA.
Autophagy Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA.
Autophagy Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA.
Autophagy Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA.
Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM 87131, USA.
Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM 87131, USA.
Proteomics Core Facility, UC Davis Genome Center, University of California, Davis, Davis, CA 95616, USA.
Proteomics Core Facility, UC Davis Genome Center, University of California, Davis, Davis, CA 95616, USA.
Department of Biomedical Sciences & Systems, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Department of Biomedical Sciences & Systems, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Autophagy Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA. Electronic address: vderetic@salud.unm.edu.

Abstract

Endomembrane damage elicits homeostatic responses including ESCRT-dependent membrane repair and autophagic removal of damaged organelles. Previous studies have suggested that these systems may act separately. Here, we show that galectin-3 (Gal3), a β-galactoside-binding cytosolic lectin, unifies and coordinates ESCRT and autophagy responses to lysosomal damage. Gal3 and its capacity to recognize damage-exposed glycans were required for efficient recruitment of the ESCRT component ALIX during lysosomal damage. Both Gal3 and ALIX were required for restoration of lysosomal function. Gal3 promoted interactions between ALIX and the downstream ESCRT-III effector CHMP4 during lysosomal repair. At later time points following lysosomal injury, Gal3 controlled autophagic responses. When this failed, as in Gal3 knockout cells, lysosomal replacement program took over through TFEB. Manifestations of this staged response, which includes membrane repair, removal, and replacement, were detected in model systems of lysosomal damage inflicted by proteopathic tau and during phagosome parasitism by Mycobacterium tuberculosis.

GrantID: R21 EB019589, Acronym: EB, Agency: NIBIB NIH HHS, Country: United States | GrantID: P30 CA118100, Acronym: CA, Agency: NCI NIH HHS, Country: United States | GrantID: R01 AI042999, Acronym: AI, Agency: NIAID NIH HHS, Country: United States | GrantID: P20 GM121176, Acronym: GM, Agency: NIGMS NIH HHS, Country: United States | GrantID: R37 AI042999, Acronym: AI, Agency: NIAID NIH HHS, Country: United States | GrantID: R01 AI111935, Acronym: AI, Agency: NIAID NIH HHS, Country: United States | GrantID: P50 GM085273, Acronym: GM, Agency: NIGMS NIH HHS, Country: United States | GrantID: R01 AI031139, Acronym: AI, Agency: NIAID NIH HHS, Country: United States | GrantID: S10 OD021801, Acronym: OD, Agency: NIH HHS, Country: United States
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