Publications

• Vasohibins encode tubulin detyrosinating activity.

  Nieuwenhuis J., Adamopoulos A., Bleijerveld O.B., Mazouzi A., Stickel E., Celie P., Altelaar M., Knipscheer P., Perrakis A., Blomen V.A., Brummelkamp T.R.

  Tubulin is subjected to a number of posttranslational modifications to generate heterogeneous microtubules. The modifications include removal and ligation of the C-terminal tyrosine of ⍺-tubulin. The enzymes responsible for detyrosination, an activity first observed 40 years ago, have remained elu ... >> More

  Tubulin is subjected to a number of posttranslational modifications to generate heterogeneous microtubules. The modifications include removal and ligation of the C-terminal tyrosine of ⍺-tubulin. The enzymes responsible for detyrosination, an activity first observed 40 years ago, have remained elusive. We applied a genetic screen in haploid human cells to find regulators of tubulin detyrosination. We identified SVBP, a peptide that regulates the abundance of vasohibins (VASH1 and VASH2). Vasohibins, but not SVBP alone, increased detyrosination of ⍺-tubulin, and purified vasohibins removed the C-terminal tyrosine of ⍺-tubulin. We found that vasohibins play a cell type-dependent role in detyrosination, although cells also contain an additional detyrosinating activity. Thus, vasohibins, hitherto studied as secreted angiogenesis regulators, constitute a long-sought missing link in the tubulin tyrosination cycle. << Less

  Science 358:1453-1456(2017) [PubMed] [EuropePMC]

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

  Aillaud C., Bosc C., Peris L., Bosson A., Heemeryck P., Van Dijk J., Le Friec J., Boulan B., Vossier F., Sanman L.E., Syed S., Amara N., Coute Y., Lafanechere L., Denarier E., Delphin C., Pelletier L., Humbert S., Bogyo M., Andrieux A., Rogowski K., Moutin M.J.

  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 ... >> More

  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. << Less

  Science 358:1448-1453(2017) [PubMed] [EuropePMC]