4.7 Article

USP17 is required for peripheral trafficking of lysosomes

Journal

EMBO REPORTS
Volume 23, Issue 4, Pages -

Publisher

WILEY
DOI: 10.15252/embr.202051932

Keywords

EGF; exocytosis; lysosome; USP17

Funding

  1. Biotechnology and Biological Sciences Research Council (BBSRC) [BB/F013647/1]
  2. BBSRC [BB/F013647/1] Funding Source: UKRI

Ask authors/readers for more resources

Expression of the deubiquitinase USP17 is induced by various stimuli and it plays important roles in cell functions, including regulation of lysosome positioning and trafficking, lysosomal protease secretion, and plasma membrane repair.
Expression of the deubiquitinase USP17 is induced by multiple stimuli, including cytokines (IL-4/6), chemokines (IL-8, SDF1), and growth factors (EGF), and several studies indicate it is required for cell proliferation and migration. However, the mechanisms via which USP17 impacts upon these cellular functions are unclear. Here, we demonstrate that USP17 depletion prevents peripheral lysosome positioning, as well as trafficking of lysosomes to the cell periphery in response to EGF stimulation. Overexpression of USP17 also increases secretion of the lysosomal protease cathepsin D. In addition, USP17 depletion impairs plasma membrane repair in cells treated with the pore-forming toxin streptolysin O, further indicating that USP17 is required for lysosome trafficking to the plasma membrane. Finally, we demonstrate that USP17 can deubiquitinate p62, and we propose that USP17 can facilitate peripheral lysosome trafficking by opposing the E3 ligase RNF26 to untether lysosomes from the ER and facilitate lysosome peripheral trafficking, lysosome protease secretion, and plasma membrane repair.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available