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

Jia, J., Claude-Taupin, A., Gu, Y., Choi, S. W., Peters, R., Bissa, B., Mudd, M. H., Allers, L., Pallikkuth, S., Lidke, K. A., Salemi, M., Phinney, B., Mari, M., Reggiori, F. & Deretic, V., 6-Jan-2020, In : Developmental Cell. 52, 1, p. 69-+ 27 p.

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  • Galectin-3 Coordinates a Cellular System for Lysosomal Repair and Removal _ Elsevier Enhanced Reader

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DOI

  • Jingyue Jia
  • Aurore Claude-Taupin
  • Yuexi Gu
  • Seong Won Choi
  • Ryan Peters
  • Bhawana Bissa
  • Michal H. Mudd
  • Lee Allers
  • Sandeep Pallikkuth
  • Keith A. Lidke
  • Michelle Salemi
  • Brett Phinney
  • Muriel Mari
  • Fulvio Reggiori
  • Vojo Deretic

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 beta-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.

Original languageEnglish
Pages (from-to)69-+
Number of pages27
JournalDevelopmental Cell
Volume52
Issue number1
Early online date29-Nov-2019
Publication statusPublished - 6-Jan-2020

    Keywords

  • PROTEIN CONJUGATION SYSTEM, ULK1 COMPLEX, AUTOPHAGOSOME FORMATION, REGULATE AUTOPHAGY, DAMAGED LYSOSOMES, ESCRT MACHINERY, MEMBRANE, MTOR, RECRUITMENT, MECHANISM

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