TrkB deubiquitylation by USP8 regulates receptor levels and BDNF-dependent neuronal differentiation.

Autor:	Martín-Rodríguez C; Departmento de Biología Celular y Patología, Instituto de Neurociencias de Castilla y León, University of Salamanca, Salamanca 37007, Spain.; Institute of Biomedical Research of Salamanca, 37007 Salamanca, Spain., Song M; Department of Life Sciences, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Korea., Anta B; Departmento de Biología Celular y Patología, Instituto de Neurociencias de Castilla y León, University of Salamanca, Salamanca 37007, Spain.; Institute of Biomedical Research of Salamanca, 37007 Salamanca, Spain., González-Calvo FJ; Departmento de Biología Celular y Patología, Instituto de Neurociencias de Castilla y León, University of Salamanca, Salamanca 37007, Spain., Deogracias R; Departmento de Biología Celular y Patología, Instituto de Neurociencias de Castilla y León, University of Salamanca, Salamanca 37007, Spain., Jing D; Department of Psychiatry, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA., Lee FS; Department of Psychiatry, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA., Arevalo JC; Departmento de Biología Celular y Patología, Instituto de Neurociencias de Castilla y León, University of Salamanca, Salamanca 37007, Spain arevalojc@usal.es.; Institute of Biomedical Research of Salamanca, 37007 Salamanca, Spain.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2020 Dec 23; Vol. 133 (24). Date of Electronic Publication: 2020 Dec 23.
DOI:	10.1242/jcs.247841
Abstrakt:	Ubiquitylation of receptor tyrosine kinases (RTKs) regulates both the levels and functions of these receptors. The neurotrophin receptor TrkB (also known as NTRK2), a RTK, is ubiquitylated upon activation by brain-derived neurotrophic factor (BDNF) binding. Although TrkB ubiquitylation has been demonstrated, there is a lack of knowledge regarding the precise repertoire of proteins that regulates TrkB ubiquitylation. Here, we provide mechanistic evidence indicating that ubiquitin carboxyl-terminal hydrolase 8 (USP8) modulates BDNF- and TrkB-dependent neuronal differentiation. USP8 binds to the C-terminus of TrkB using its microtubule-interacting domain (MIT). Immunopurified USP8 deubiquitylates TrkB in vitro , whereas knockdown of USP8 results in enhanced ubiquitylation of TrkB upon BDNF treatment in neurons. As a consequence of USP8 depletion, TrkB levels and its activation are reduced. Moreover, USP8 protein regulates the differentiation and correct BDNF-dependent dendritic formation of hippocampal neurons in vitro and in vivo We conclude that USP8 positively regulates the levels and activation of TrkB, modulating BDNF-dependent neuronal differentiation.This article has an associated First Person interview with the first author of the paper. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2020. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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