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Vasohibins/SVBP are tubulin carboxypeptidases (TCPs) that regulate neuron differentiation.

Authors :
Aillaud C
Bosc C
Peris L
Bosson A
Heemeryck P
Van Dijk J
Le Friec J
Boulan B
Vossier F
Sanman LE
Syed S
Amara N
Couté Y
Lafanechère L
Denarier E
Delphin C
Pelletier L
Humbert S
Bogyo M
Andrieux A
Rogowski K
Moutin MJ
Source :
Science (New York, N.Y.) [Science] 2017 Dec 15; Vol. 358 (6369), pp. 1448-1453. Date of Electronic Publication: 2017 Nov 16.
Publication Year :
2017

Abstract

Reversible detyrosination of α-tubulin is crucial to microtubule dynamics and functions, and defects have been implicated in cancer, brain disorganization, and cardiomyopathies. The identity of the tubulin tyrosine carboxypeptidase (TCP) responsible for detyrosination has remained unclear. We used chemical proteomics with a potent irreversible inhibitor to show that the major brain TCP is a complex of vasohibin-1 (VASH1) with the small vasohibin binding protein (SVBP). VASH1 and its homolog VASH2, when complexed with SVBP, exhibited robust and specific Tyr/Phe carboxypeptidase activity on microtubules. Knockdown of vasohibins or SVBP and/or inhibitor addition in cultured neurons reduced detyrosinated α-tubulin levels and caused severe differentiation defects. Furthermore, knockdown of vasohibins disrupted neuronal migration in developing mouse neocortex. Thus, vasohibin/SVBP complexes represent long-sought TCP enzymes.<br /> (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Details

Language :
English
ISSN :
1095-9203
Volume :
358
Issue :
6369
Database :
MEDLINE
Journal :
Science (New York, N.Y.)
Publication Type :
Academic Journal
Accession number :
29146868
Full Text :
https://doi.org/10.1126/science.aao4165