Late endosomes promote microglia migration via cytosolic translocation of immature protease cathD
Open Access
- 11 December 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 6 (50), eaba5783
- https://doi.org/10.1126/sciadv.aba5783
Abstract
Organelle transport requires dynamic cytoskeleton remodeling, but whether cytoskeletal dynamics are, in turn, regulated by organelles remains elusive. Here, we demonstrate that late endosomes, a type of prelysosomal organelles, facilitate actin-cytoskeleton remodeling via cytosolic translocation of immature protease cathepsin D (cathD) during microglia migration. After cytosolic translocation, late endosome–derived cathD juxtaposes actin filaments at the leading edge of lamellipodia. Suppressing cathD expression or blocking its cytosolic translocation impairs the maintenance but not the initiation of lamellipodial extension. Moreover, immature cathD balances the activity of the actin-severing protein cofilin to maintain globular-actin (G-actin) monomer pool for local actin recycling. Our study identifies cathD as a key lysosomal molecule that unconventionally contributes to actin cytoskeleton remodeling via cytosolic translocation during adenosine triphosphate–evoked microglia migration.Funding Information
- National Natural Science Foundation of China (31490590,81821091,81527901,91832000)
- National Natural Science Foundation of China (31501128)
- National Natural Science Foundation of China (31871039)
- Science and Technology Planning Project of Guangdong Province (2018B030331001)
- National Key Research and Development Program of China Stem Cell and Translational Research (2016YFA0501000)
- Chinese Ministry of Education Project 111 Program (B13026)
- National Natual Science Foundation of China (81761138044)
This publication has 50 references indexed in Scilit:
- Cell mechanics control rapid transitions between blebs and lamellipodia during migrationProceedings of the National Academy of Sciences of the United States of America, 2012
- Microglial migration mediated by ATP-induced ATP release from lysosomesCell Research, 2012
- Cell adhesion: integrating cytoskeletal dynamics and cellular tensionNature Reviews Molecular Cell Biology, 2010
- Hsp70 stabilizes lysosomes and reverts Niemann–Pick disease-associated lysosomal pathologyNature, 2010
- Lysosomes as “Suicide Bags” in Cell Death: Myth or Reality?Online Journal of Public Health Informatics, 2009
- Cathepsin D: A cellular roadmapBiochemical and Biophysical Research Communications, 2008
- Cathepsin D—Many functions of one aspartic proteaseCritical Reviews in Oncology/Hematology, 2008
- Shaping cups into phagosomes and macropinosomesNature Reviews Molecular Cell Biology, 2008
- Heat Shock Protein 70 Promotes Cell Survival by Inhibiting Lysosomal Membrane PermeabilizationThe Journal of Experimental Medicine, 2004
- A General Role for Rab27a in Secretory CellsMolecular Biology of the Cell, 2004