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The USP12/46 deubiquitinases protect integrins from ESCRT-mediated lysosomal degradation

Yu, Kaikai, Wang, Guan M, Guo, Shiny Shengzhen, Bassermann, Florian, Fässler, Reinhard·2024·EMBO Reports
DOI 10.1038/s44319-024-00300-9PMC PMC11624278

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Abstract

The functions of integrins are tightly regulated via multiple mechanisms including trafficking and degradation. Integrins are repeatedly internalized, routed into the endosomal system and either degraded by the lysosome or recycled back to the plasma membrane. The ubiquitin system dictates whether internalized proteins are degraded or recycled. Here, we use a genetic screen and proximity-dependent biotin identification to identify deubiquitinase(s) that control integrin surface levels. We find that a ternary deubiquitinating complex, comprised of USP12 (or the homologous USP46), WDR48 and WDR20, stabilizes β1 integrin (Itgb1) by preventing ESCRT-mediated lysosomal degradation. Mechanistically, the USP12/46-WDR48-WDR20 complex removes ubiquitin from the cytoplasmic tail of internalized Itgb1 in early endosomes, which in turn prevents ESCRT-mediated sorting and Itgb1 degradation.

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Metadata

Authors
Yu, K., Wang, G. M., Guo, S. S., Bassermann, F., & Fässler, R.
ORCID
Venue
EMBO Reports
Publisher
Springer Science and Business Media LLC
Published
2024-11-06
Volume
25
Issue
12
ISSN
  • 1469-221X
  • 1469-3178
DOI
10.1038/s44319-024-00300-9
PMC
PMC11624278
Cited by
10
References
1
Language
en
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