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Article Dans Une Revue Science Année : 2017

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

Leticia Peris
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Marie-Jo Moutin

Résumé

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.

Domaines

Neurobiologie
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Dates et versions

hal-02345845 , version 1 (04-11-2022)

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Chrystelle Aillaud, Christophe Bosc, Leticia Peris, Anouk Bosson, Pierre Heemeryck, et al.. Vasohibins/SVBP are tubulin carboxypeptidases (TCPs) that regulate neuron differentiation. Science, 2017, 358 (6369), pp.1448-1453. ⟨10.1126/science.aao4165⟩. ⟨hal-02345845⟩
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