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Loss of the canonical spindle orientation function in the Pins/LGN homolog AGS3.


ABSTRACT: In many cell types, mitotic spindle orientation relies on the canonical "LGN complex" composed of Pins/LGN, Mud/NuMA, and G?i 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 G?iin 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.

SUBMITTER: Saadaoui M 

PROVIDER: S-EPMC5579374 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Loss of the canonical spindle orientation function in the Pins/LGN homolog AGS3.

Saadaoui Mehdi M   Konno Daijiro D   Loulier Karine K   Goiame Rosette R   Jadhav Vaibhav V   Mapelli Marina M   Matsuzaki Fumio F   Morin Xavier X  

EMBO reports 20170706 9


In many cell types, mitotic spindle orientation relies on the canonical "LGN complex" composed of Pins/LGN, Mud/NuMA, and Gα<sub>i</sub> subunits. Membrane localization of this complex recruits motor force generators that pull on astral microtubules to orient the spindle. <i>Drosophila</i> 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 cont  ...[more]

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