Loss of the canonical spindle orientation function in the Pins/LGN homolog AGS3
Loss of the canonical spindle orientation function in the Pins/LGN homolog AGS3
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DOI：
10.15252/embr.201643048
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发表时间：
2017-07
期刊：
影响因子：
7.7
通讯作者：
M. Saadaoui;D. Konno;K. Loulier;Rosette Goiame;Vaibhav Jadhav;M. Mapelli;F. Matsuzaki;X. Morin
中科院分区：
文献类型：
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作者：
M. Saadaoui;D. Konno;K. Loulier;Rosette Goiame;Vaibhav Jadhav;M. Mapelli;F. Matsuzaki;X. Morin
在许多细胞类型中，有丝分裂纺锤体取向依赖于由Pins/LGN、Mud/NuMA和Gαi亚基组成的典型“LGN复合体”。这个复合体的膜定位招募马达力发生器，拉动星形微管来定位纺锤体。果蝇Pins与其两个脊椎动物同源物LGN和AGS 3共享高度保守的功能结构域。虽然引脚和LGN在定向师的作用被广泛记录，AGS 3的参与仍然存在争议。在这里，我们表明，AGS 3是不需要在小鼠新皮层的神经祖细胞的平面分裂。AGS 3不被募集到细胞皮质，也不挽救LGN功能的丧失。尽管在体外与NuMA和Gαi的保守相互作用，但体内LGN和AGS 3功能结构域的比较揭示了这些相互作用介导纺锤体取向功能的能力的意外差异。最后，我们发现果蝇Pins无法替代脊椎动物中LGN功能的丧失，这突出表明Pins/LGN复合物组分之间相互作用的物种特异性调节对于体内纺锤体取向至关重要。
In many cell types, mitotic spindle orientation relies on the canonical “LGN complex” composed of Pins/LGN, Mud/NuMA, and Gαi subunits. Membrane localization of this complex recruits motor force generators that pull on astral microtubules to orient the spindle. Drosophila Pins shares highly conserved functional domains with its two vertebrate homologs LGN and AGS3. Whereas the role of Pins and LGN in oriented divisions is extensively documented, involvement of AGS3 remains controversial. Here, we show that AGS3 is not required for planar divisions of neural progenitors in the mouse neocortex. AGS3 is not recruited to the cell cortex and does not rescue LGN loss of function. Despite conserved interactions with NuMA and Gαi in vitro, comparison of LGN and AGS3 functional domains in vivo reveals unexpected differences in the ability of these interactions to mediate spindle orientation functions. Finally, we find that Drosophila Pins is unable to substitute for LGN loss of function in vertebrates, highlighting that species‐specific modulations of the interactions between components of the Pins/LGN complex are crucial in vivo for spindle orientation.