title: NuMA interacts with phosphoinositides and links the mitotic spindle with the plasma membrane.
abstract: The positioning and the elongation of the mitotic spindle must be carefully regulated. In human cells, the evolutionary conserved proteins LGN/Gαi1-3 anchor the coiled-coil protein NuMA and dynein to the cell cortex during metaphase, thus ensuring proper spindle positioning. The mechanisms governing cortical localization of NuMA and dynein during anaphase remain more elusive. Here, we report that LGN/Gαi1-3 are dispensable for NuMA-dependent cortical dynein enrichment during anaphase. We further establish that NuMA is excluded from the equatorial region of the cell cortex in a manner that depends on the centralspindlin components CYK4 and MKLP1. Importantly, we reveal that NuMA can directly associate with PtdInsP (PIP) and PtdInsP2 (PIP2) phosphoinositides in vitro. Furthermore, chemical or enzymatic depletion of PIP/PIP2 prevents NuMA cortical localization during mitosis, and conversely, increasing PIP2 levels augments mitotic cortical NuMA. Overall, our study uncovers a novel function for plasma membrane phospholipids in governing cortical NuMA distribution and thus the proper execution of mitosis.
authors.affiliation: School of Life Sciences, Swiss Institute for Experimental Cancer Research (ISREC), Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
authors.forename: Sachin
authors.initials: S
authors.lastname: Kotak
authors.affiliation: School of Life Sciences, Swiss Institute for Experimental Cancer Research (ISREC), Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
authors.forename: Coralie
authors.initials: C
authors.lastname: Busso
authors.affiliation: School of Life Sciences, Swiss Institute for Experimental Cancer Research (ISREC), Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland Pierre.Gonczy@epfl.ch.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gönczy
mesh_terms: D000705:Anaphase; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002462:Cell Membrane / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008677:Metaphase; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008938:Mitosis; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; C102754:GPSM2 protein, human; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; C092935:KIF23 protein, human; D008869:Microtubule-Associated Proteins; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D010716:Phosphatidylinositols; C115995:mgcRacGAP; D004398:Dyneins; C498819:GNAI3 protein, human; D019206:GTP-Binding Protein alpha Subunits, Gi-Go
keywords: NuMA; dynein; phosphoinositides; spindle elongation; spindle positioning