Laboratory of Cell Regulation UK, London Research Institute, London, UK.
EMBO Rep. 2014 Feb;15(2):175-84. doi: 10.1002/embr.201337929. Epub 2014 Jan 7.
Anchoring microtubules to the centrosome is critical for cell geometry and polarity, yet the molecular mechanism remains unknown. Here we show that the conserved human Msd1/SSX2IP is required for microtubule anchoring. hMsd1/SSX2IP is delivered to the centrosome in a centriolar satellite-dependent manner and binds the microtubule-nucleator γ-tubulin complex. hMsd1/SSX2IP depletion leads to disorganised interphase microtubules and misoriented mitotic spindles with reduced length and intensity. Furthermore, hMsd1/SSX2IP is essential for ciliogenesis, and during zebrafish embryogenesis, knockdown of its orthologue results in ciliary defects and disturbs left-right asymmetry. We propose that the Msd1 family comprises conserved microtubule-anchoring proteins.
将微管锚定到中心体对于细胞的形态和极性至关重要,但分子机制尚不清楚。在这里,我们发现保守的人源 Msd1/SSX2IP 对于微管锚定是必需的。hMsd1/SSX2IP 以中心粒卫星依赖的方式被递送到中心体,并与微管起始因子 γ-微管蛋白复合物结合。hMsd1/SSX2IP 的耗竭导致有丝分裂纺锤体的微管排列紊乱,方向错误,长度和强度降低。此外,hMsd1/SSX2IP 对于纤毛发生是必需的,在斑马鱼胚胎发生过程中,其同源物的敲低导致纤毛缺陷,并扰乱左右不对称性。我们提出 Msd1 家族包含保守的微管锚定蛋白。