Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Mol Biol Cell. 2012 Jun;23(11):2122-30. doi: 10.1091/mbc.E11-11-0931. Epub 2012 Apr 4.
The diverse populations of microtubule polymers in cells are functionally distinguished by different posttranslational modifications, including polyglutamylation. Polyglutamylation is enriched on subsets of microtubules including those found in the centrioles, mitotic spindle, and cilia. However, whether this modification alters intrinsic microtubule dynamics or affects extrinsic associations with specific interacting partners remains to be determined. Here we identify the microtubule-binding protein centriole and spindle-associated protein (CSAP), which colocalizes with polyglutamylated tubulin to centrioles, spindle microtubules, and cilia in human tissue culture cells. Reducing tubulin polyglutamylation prevents CSAP localization to both spindle and cilia microtubules. In zebrafish, CSAP is required for normal brain development and proper left-right asymmetry, defects that are qualitatively similar to those reported previously for depletion of polyglutamylation-conjugating enzymes. We also find that CSAP is required for proper cilia beating. Our work supports a model in which polyglutamylation can target selected microtubule-associated proteins, such as CSAP, to microtubule subpopulations, providing specific functional capabilities to these populations.
细胞中微管聚合物的多样化群体通过不同的翻译后修饰来区分功能，包括多聚谷氨酸化。多聚谷氨酸化在中心体、有丝分裂纺锤体和纤毛中的微管包括那些微管中富集。然而，这种修饰是否改变了微管的固有动力学，或者是否影响了与特定相互作用伙伴的外在关联，仍有待确定。在这里，我们鉴定了微管结合蛋白中心体和纺锤体相关蛋白 (CSAP)，它与人组织培养细胞中的中心体、纺锤体微管和纤毛中的多聚谷氨酸化微管蛋白共定位。减少微管多聚谷氨酸化会阻止 CSAP 定位于纺锤体和纤毛微管。在斑马鱼中，CSAP 对于正常的大脑发育和正确的左右不对称是必需的，这些缺陷与先前报道的多聚谷氨酸化连接酶耗竭的缺陷在性质上相似。我们还发现 CSAP 对于正确的纤毛跳动是必需的。我们的工作支持这样一种模型，即多聚谷氨酸化可以将选定的微管相关蛋白，如 CSAP，靶向微管亚群，为这些群体提供特定的功能能力。
