Tubulin carboxypeptidase identity revealed Enzymes of the α-tubulin detyrosination/tyrosination cycle create landmarks on microtubules that are essential for their multiple cellular functions and are altered in disease. Tubulin carboxypeptidases (TCPs) responsible for detyrosination have remained elusive for 40 years (see the Perspective by Akhmanova and Maiato). Aillaud et al. identified vasohibins as enzymes that perform the TCP function and found that their small interacting partner SBVP was essential for their activity. Vasohibin/SVBP complexes were involved in neuron polarization and brain cortex development. The authors also developed an inhibitor targeting this family of enzymes. Using a completely different strategy, Nieuwenhuis et al. also showed that vasohibins can remove the C-terminal tyrosine of α-tubulin. Science, this issue p. 1448, p. 1453; see also p. 1381 The long-sought tubulin carboxypeptidases responsible for microtubule detyrosination have now been discovered. 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.

中文翻译：

---

血管抑制素编码微管蛋白去酪氨酸活性

微管蛋白羧肽酶的特性揭示了 α-微管蛋白去酪氨酸化/酪氨酸化循环的酶在微管上创造了标志，这对其多种细胞功能至关重要，并在疾病中发生改变。40 年来，负责去酪氨酸化的微管蛋白羧肽酶 (TCP) 一直难以捉摸（参见 Akhmanova 和 Maiato 的观点）。艾洛等人。确定血管抑制素是执行 TCP 功能的酶，并发现它们的小相互作用伙伴 SBVP 对其活性至关重要。血管抑制素/SVBP 复合物参与神经元极化和大脑皮层发育。作者还开发了一种针对该酶家族的抑制剂。Nieuwenhuis 等人使用完全不同的策略。还表明血管抑制素可以去除 α-微管蛋白的 C 端酪氨酸。科学，这个问题 p。1448, 页。第1453章 另见第。1381 现在已经发现了负责微管去酪氨酸化的长期寻找的微管蛋白羧肽酶。微管蛋白经过许多翻译后修饰以生成异质微管。修饰包括去除和连接⍺-微管蛋白的 C 端酪氨酸。负责去酪氨酸化的酶是 40 年前首次观察到的一种活动，但仍然难以捉摸。我们在单倍体人类细胞中应用遗传筛选来寻找微管蛋白去酪氨酸化的调节剂。我们鉴定了 SVBP，一种调节血管抑制素（VASH1 和 VASH2）丰度的肽。血管抑制素，但不是单独的 SVBP，增加了⍺-微管蛋白的去酪氨酸化，纯化的血管抑制素去除了⍺-微管蛋白的 C 端酪氨酸。我们发现血管抑制素在去酪氨酸化过程中发挥细胞类型依赖性作用，尽管细胞还含有额外的去酪氨酸活性。因此，迄今为止被研究为分泌性血管生成调节剂的血管抑制素构成了微管蛋白酪氨酸化循环中长期寻找的缺失环节。