Post-endocytotic Deubiquitination and Degradation of the MetabotropicAminobutyric Acid Receptor by the Ubiquitin-specific Protease 14

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F16%3A00471850" target="_blank" >RIV/68378050:_____/16:00471850 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1074/jbc.M115.686907" target="_blank" >http://dx.doi.org/10.1074/jbc.M115.686907</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1074/jbc.M115.686907" target="_blank" >10.1074/jbc.M115.686907</a>

Result language

angličtina

Original language name

Post-endocytotic Deubiquitination and Degradation of the MetabotropicAminobutyric Acid Receptor by the Ubiquitin-specific Protease 14

Original language description

Mechanisms controlling the metabotropicaminobutyric acid receptor (GABA(B)) cell surface stability are still poorly understood. In contrast with many other G protein-coupled receptors (GPCR), it is not subject to agonist-promoted internalization, but is constitutively internalized and rapidly down-regulated. In search of novel interacting proteins regulating receptor fate, we report that the ubiquitin-specific protease 14 (USP14) interacts with the GABA(B(1b)) subunit's second intracellular loop. Probing the receptor for ubiquitination using bioluminescence resonance energy transfer (BRET), we detected a constitutive and phorbol 12-myristate 13-acetate (PMA)-induced ubiquitination of the receptor at the cell surface. PMA also increased internalization and accelerated receptor degradation. Overexpression of USP14 decreased ubiquitination while treatment with a small molecule inhibitor of the deubiquitinase (IU1) increased receptor ubiquitination. Treatment with the internalization inhibitor Dynasore blunted both USP14 and IU1 effects on the receptor ubiquitination state, suggesting a post-endocytic site of action. Overexpression of USP14 also led to an accelerated degradation of GABA(B) in a catalytically independent fashion. We thus propose a model whereby cell surface ubiquitination precedes endocytosis, after which USP14 acts as an ubiquitin-binding protein that targets the ubiquitinated receptor to lysosomal degradation and promotes its deubiquitination.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

<a href="/en/project/GAP303%2F12%2F2408" target="_blank" >GAP303/12/2408: Functional Consequences of Metabotropic Glutamate Receptor 1a and 1b Splice Variants Assembly in Heterodimeric Complexes</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

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Volume of the periodical

291

Issue of the periodical within the volume

13

Country of publishing house

US - UNITED STATES

Number of pages

15

Pages from-to

7156-7170

UT code for WoS article

000373299700048

EID of the result in the Scopus database

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