Katanin-like protein Katnal2 is required for ciliogenesis and brain development in Xenopus embryos.

Katanin-like protein Katnal2 is required for ciliogenesis and brain development in Xenopus embryos.
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DOI:
10.1016/j.ydbio.2018.08.002
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发表时间:
2018-10-15
影响因子:
2.7
通讯作者:
Santama N
Santama N
中科院分区:
生物学3区
文献类型:
--
作者:
Willsey HR;Walentek P;Exner CRT;Xu Y;Lane AB;Harland RM;Heald R;Santama N

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微管重塑是细胞和发育过程的基础形态发生变化和许多亚细胞结构的形成至关重要。Katanins是一种保守的微管切割酶,对纺锤体组装、纤毛发生、细胞分裂和细胞运动至关重要。我们最近发现,一个相关的蛋白质,Katanin样2(KATNAL 2),同样需要在培养的小鼠细胞胞质分裂,细胞周期的进展,和纤毛发生。然而,它的发育表达模式,定位,并在器官发生过程中的体内作用还没有得到表征。在这里,我们使用非洲爪蟾胚胎揭示Katnal 2(1)在整个胚胎发育过程中广泛表达于纤毛和神经组织;(2)定位于基体,纤毛轴丝,中心粒和有丝分裂纺锤体;(3)是纤毛发生和大脑发育所必需的。由于人类KATNAL 2是自闭症谱系障碍的风险基因,我们的功能数据表明,非洲爪蟾可能是一个相关的系统,了解该基因的突变与自闭症的关系和发病机制的潜在分子机制。
Microtubule remodeling is critical for cellular and developmental processes underlying morphogenetic changes and for the formation of many subcellular structures. Katanins are conserved microtubule severing enzymes that are essential for spindle assembly, ciliogenesis, cell division, and cellular motility. We have recently shown that a related protein, Katanin-like 2 (KATNAL2), is similarly required for cytokinesis, cell cycle progression, and ciliogenesis in cultured mouse cells. However, its developmental expression pattern, localization, and in vivo role during organogenesis have yet to be characterized. Here, we used Xenopus embryos to reveal that Katnal2 (1) is expressed broadly in ciliated and neurogenic tissues throughout embryonic development; (2) is localized to basal bodies, ciliary axonemes, centrioles, and mitotic spindles; and (3) is required for ciliogenesis and brain development. Since human KATNAL2 is a risk gene for autism spectrum disorders, our functional data suggest that Xenopus may be a relevant system for understanding the relationship of mutations in this gene to autism and the underlying molecular mechanisms of pathogenesis.
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