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Updated: Nov 26, 2025

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Late endosomes promote microglia migration via cytosolic translocation of immature protease cathD
Yi-Jun Liu1, Ting Zhang2, Daxiao Cheng2
1Department of Neurobiology, NHC and CAMS Key Laboratory of Medical Neurobiology, School of Brain Science and Brian Medicine, and the MOE Frontier Science Center for Brain Research and Brain-Machine Integration, Zhejiang University School of Medicine, Hangzhou 310058, China. duanshumin@zju.edu.cn xiaodongwang@zju.edu.cn margareth@shanghaitech.edu.cn yjliu@zju.edu.cn.
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.
Insights
Late endosomes regulate actin cytoskeleton remodeling through the translocation of immature cathepsin D (cathD) during microglia migration. This process is crucial for maintaining cell movement and actin dynamics.
Area of Science:
- Cell Biology
- Cytoskeleton Dynamics
- Organelle Biology
Background:
- Organelle transport relies on cytoskeleton remodeling.
- The reciprocal regulation of cytoskeletal dynamics by organelles is not well understood.
Purpose of the Study:
- To investigate the role of late endosomes in regulating actin cytoskeleton dynamics.
- To identify specific molecules involved in organelle-mediated cytoskeletal remodeling during microglia migration.
Main Methods:
- Studied microglia migration using live-cell imaging.
- Investigated the role of cathepsin D (cathD) and its translocation.
- Analyzed the impact of cathD manipulation on actin dynamics and cofilin activity.
Main Results:
- Late endosomes facilitate actin remodeling via cytosolic translocation of immature cathD.
- Translocated cathD localizes to the leading edge of lamellipodia.
- Suppression of cathD impairs lamellipodial maintenance and balances cofilin activity, maintaining the globular-actin (G-actin) pool.
Conclusions:
- Immature cathD, translocated from late endosomes, is a key regulator of actin cytoskeleton remodeling.
- This unconventional role of cathD is essential for sustained microglia migration.
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