The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor recycling and resensitization.

Published

Journal Article

Agonist-induced ubiquitination of the beta(2) adrenergic receptor (beta(2)AR) functions as an important post-translational modification to sort internalized receptors to the lysosomes for degradation. We now show that this ubiquitination is reversed by two deubiquitinating enzymes, ubiquitin-specific proteases (USPs) 20 and 33, thus, inhibiting lysosomal trafficking when concomitantly promoting receptor recycling from the late-endosomal compartments as well as resensitization of recycled receptors at the cell surface. Dissociation of constitutively bound endogenously expressed USPs 20 and 33 from the beta(2)AR immediately after agonist stimulation and reassociation on prolonged agonist treatment allows receptors to first become ubiquitinated and then deubiquitinated, thus, providing a 'trip switch' between degradative and recycling pathways at the late-endosomal compartments. Thus, USPs 20 and 33 serve as novel regulators that dictate both post-endocytic sorting as well as the intensity and extent of beta(2)AR signalling from the cell surface.

Full Text

Duke Authors

Cited Authors

  • Berthouze, M; Venkataramanan, V; Li, Y; Shenoy, SK

Published Date

  • June 17, 2009

Published In

Volume / Issue

  • 28 / 12

Start / End Page

  • 1684 - 1696

PubMed ID

  • 19424180

Pubmed Central ID

  • 19424180

Electronic International Standard Serial Number (EISSN)

  • 1460-2075

Digital Object Identifier (DOI)

  • 10.1038/emboj.2009.128

Language

  • eng

Conference Location

  • England