TY - JOUR
T1 - Loss of the canonical spindle orientation function in the Pins/LGN homolog AGS3
AU - Saadaoui, Mehdi
AU - Konno, Daijiro
AU - Loulier, Karine
AU - Goiame, Rosette
AU - Jadhav, Vaibhav
AU - Mapelli, Marina
AU - Matsuzaki, Fumio
AU - Morin, Xavier
N1 - Funding Information:
We thank Samuel Tozer and Florencia di Pietro for helpful discussions on this project. We acknowledge Benjamin Mathieu and the IBENS imaging platform for excellent assistance. Imaging equipment was acquired through the generous help of the Neuropôle de Recherche Francilien. Work in X.Morin's laboratory was supported by an INSERM Avenir Grant (R08221JS), the Fondation pour la Recherche Medicale (FRM DEQ20150331735), the Fondation ARC (ARC Livespin, SFI20111203877), the Agence Nationale pour la Recherche (ANR-12-BSV2-0014-01), Cancéropôle Ile-de-France (2013-2-INV-05), and FRC (AOE-9 2014). M. Saadaoui was the recipient of postdoctoral fellowships from INSERM (Avenir), NeRF, and ANR. This work has received support under the program “Investissements d'Avenir” launched by the French Government and implemented by the ANR, with the references: ANR-10-LABX-54 MEMO LIFE and ANR-11-IDEX-0001-02 PSL* Research University.
Publisher Copyright:
© 2017 The Authors
PY - 2017/9
Y1 - 2017/9
N2 - 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.
AB - 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.
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U2 - 10.15252/embr.201643048
DO - 10.15252/embr.201643048
M3 - Article
C2 - 28684399
AN - SCOPUS:85021798479
VL - 18
SP - 1509
EP - 1520
JO - EMBO Reports
JF - EMBO Reports
SN - 1469-221X
IS - 9
ER -