title: Cortical dynein is critical for proper spindle positioning in human cells.
abstract: Correct spindle positioning is fundamental for proper cell division during development and in stem cell lineages. Dynein and an evolutionarily conserved ternary complex (nuclear mitotic apparatus protein [NuMA]-LGN-Gα in human cells and LIN-5-GPR-1/2-Gα in Caenorhabditis elegans) are required for correct spindle positioning, but their relationship remains incompletely understood. By analyzing fixed specimens and conducting live-imaging experiments, we uncovered that appropriate levels of ternary complex components are critical for dynein-dependent spindle positioning in HeLa cells and C. elegans embryos. Moreover, using mutant versions of Gα in both systems, we established that dynein acts at the membrane to direct spindle positioning. Importantly, we identified a region within NuMA that mediates association with dynein. By using this region to target dynein to the plasma membrane, we demonstrated that the mere presence of dynein at that location is sufficient to direct spindle positioning in HeLa cells. Overall, we propose a model in which the ternary complex serves to anchor dynein at the plasma membrane to ensure correct spindle positioning.
authors.affiliation: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology Lausanne, Lausanne CH-1015, Switzerland.
authors.forename: Sachin
authors.initials: S
authors.lastname: Kotak
authors.forename: Coralie
authors.initials: C
authors.lastname: Busso
authors.forename: Pierre
authors.initials: P
authors.lastname: Gönczy
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018797:Cell Cycle Proteins; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004398:Dyneins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D004398:Dyneins