The Distribution of Active Force Generators Controls Mitotic Spindle Position

During unequal cell divisions a mitotic spindle is eccentrically positioned before cell cleavage. To determine the basis of the net force imbalance that causes spindle displacement in one-cell Caenorhabditis elegans embryos, we fragmented centrosomes with an ultraviolet laser. Analysis of the mean and variance of fragment speeds suggests that the force imbalance is due to a larger number of force generators pulling on astral microtubules of the posterior aster relative to the anterior aster. Moreover, activation of heterotrimeric guanine nucleotide– binding protein (Gprotein) α subunits is required to generate these astral forces.

[1]  P. Gönczy.  Mechanisms of spindle positioning: focus on flies and worms. , 2002, Trends in cell biology.

[2]  D. Baillie,et al.  A Formin Homology Protein and a Profilin Are Required for Cytokinesis and Arp2/3-Independent Assembly of Cortical Microfilaments in C. elegans , 2002, Current Biology.

[3]  J. Ahringer,et al.  Distinct roles for Gα and Gβγ in regulating spindle position and orientation in Caenorhabditis elegans embryos , 2001, Nature Cell Biology.

[4]  Anthony A. Hyman,et al.  Polarity controls forces governing asymmetric spindle positioning in the Caenorhabditis elegans embryo , 2001, Nature.

[5]  D. Albertson.  Formation of the first cleavage spindle in nematode embryos. , 1984, Developmental biology.

[6]  Pierre Gönczy,et al.  Translation of Polarity Cues into Asymmetric Spindle Positioning in Caenorhabditis elegans Embryos , 2003, Science.

[7]  J. Schmee.  Applied Statistics—A Handbook of Techniques , 1984 .

[8]  Ira Herskowitz,et al.  Mechanisms of asymmetric cell division: Two Bs or not two Bs, that is the question , 1992, Cell.

[9]  Sebastian A. Leidel,et al.  Functional genomic analysis of cell division in C. elegans using RNAi of genes on chromosome III , 2000, Nature.

[10]  J. Ahringer,et al.  Asymmetrically Distributed C. elegans Homologs of AGS3/PINS Control Spindle Position in the Early Embryo , 2003, Current Biology.

[11]  F. Sigworth,et al.  Sodium channels in nerve apparently have two conductance states , 1977, Nature.

[12]  Lesilee S. Rose,et al.  PAR-dependent and geometry-dependent mechanisms of spindle positioning , 2003, The Journal of cell biology.

[13]  G. Seydoux,et al.  Anterior-Posterior Polarity in C. elegans and Drosophila--PARallels and Differences , 2002, Science.

[14]  R. Vallee,et al.  Dynein at the cortex. , 2002, Current opinion in cell biology.

[15]  P. Gönczy,et al.  The kinetically dominant assembly pathway for centrosomal asters in Caenorhabditis elegans is γ-tubulin dependent , 2002, The Journal of cell biology.

[16]  G. C. Rogers,et al.  Microtubule motors in mitosis , 2000, Nature.

[17]  S. van den Heuvel,et al.  A complex of LIN-5 and GPR proteins regulates G protein signaling and spindle function in C elegans. , 2003, Genes & development.

[18]  Bruce Bowerman,et al.  Heads or tails: cell polarity and axis formation in the early Caenorhabditis elegans embryo. , 2002, Developmental cell.

[19]  W. Chia,et al.  Apical Complex Genes Control Mitotic Spindle Geometry and Relative Size of Daughter Cells in Drosophila Neuroblast and pI Asymmetric Divisions , 2003, Cell.

[20]  D. Pellman,et al.  Search, capture and signal: games microtubules and centrosomes play. , 2001, Journal of cell science.

[21]  F. Sigworth.  The variance of sodium current fluctuations at the node of Ranvier , 1980, The Journal of physiology.

[22]  T. Mitchison,et al.  Mitosis: a history of division , 2001, Nature Cell Biology.

[23]  Anthony A. Hyman,et al.  Dynamics and mechanics of the microtubule plus end , 2022 .