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USP17 is required for peripheral trafficking of lysosomes
Author(s) -
Lin Jia,
McCann Aidan P,
Sereesongsaeng Naphannop,
Burden Jonathan M,
Alsa’d Alhareth A,
Burden Roberta E,
Micu Ileana,
Williams Richard,
Van Schaeybroeck Sandra,
Evergren Emma,
Mullan Paul,
Simpson Jeremy C,
Scott Christopher J,
Burrows James F
Publication year - 2022
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202051932
Subject(s) - lysosome , microbiology and biotechnology , cathepsin , streptolysin , secretion , cathepsin d , biology , chemistry , biochemistry , enzyme , bacterial protein , gene
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.