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

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Science  16 Nov 2017:
eaao4165
DOI: 10.1126/science.aao4165

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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 unique 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. Knock down of vasohibins or SVBP and/or inhibitor addition in cultured neurons reduced detyrosinated α-tubulin levels and caused severe differentiation defects. Furthermore, knock down of vasohibins disrupted neuronal migration in developing mouse neocortex. Thus vasohibin/SVBP complexes represent long sought TCP enzymes.

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