CSAP localizes to polyglutamylated microtubules and promotes proper cilia function and zebrafish development.
CSAP localizes to polyglutamylated microtubules and promotes proper cilia function and zebrafish development.
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DOI：
10.1091/mbc.e11-11-0931
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发表时间：
2012-06
影响因子：
3.3
通讯作者：
Cheeseman IM
中科院分区：
文献类型：
--
作者：
Backer CB;Gutzman JH;Pearson CG;Cheeseman IM
微管的亚群被多聚谷氨酰化修饰，但这种修饰的确切功能尚不清楚。微管结合蛋白，CSAP，被确定为与多聚谷氨酰化微管蛋白共定位。在斑马鱼中，CSAP是正常的大脑发育和适当的左右不对称所必需的。细胞中微管聚合物的不同群体在功能上通过不同的翻译后修饰（包括多聚谷氨酰化）来区分。多聚谷氨酰化富集在微管亚群上，包括在中心粒、有丝分裂纺锤体和纤毛中发现的那些。然而，这种修饰是否会改变内在的微管动力学或影响与特定相互作用伙伴的外在关联仍有待确定。在这里，我们确定了微管结合蛋白中心粒和纺锤体相关蛋白（CSAP），它与多聚谷氨酰化微管蛋白共定位于人类组织培养细胞的中心粒，纺锤体微管和纤毛。减少微管蛋白多聚谷氨酰化可防止CSAP定位于纺锤体和纤毛微管。在斑马鱼中，CSAP是正常的大脑发育和适当的左右不对称所必需的，这些缺陷与先前报道的多聚谷氨酰化缀合酶耗尽的缺陷在质量上类似。我们还发现，CSAP是需要适当的纤毛殴打。我们的工作支持一种模型，其中多聚谷氨酰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。
Subsets of microtubules are modified by polyglutamylation, but the precise function of this modification is unknown. A microtubule-binding protein, CSAP, is identified that colocalizes with polyglutamylated tubulin. In zebrafish, CSAP is required for normal brain development and proper left–right asymmetry. 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.