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Translation of Polarity Cues into Asymmetric Spindle Positioning in Caenorhabditis elegans Embryos
Kelly Colombo,1Stephan W. Grill,2Randall J. Kimple,3Francis S. Willard,3David P. Siderovski,3Pierre Gönczy1*
Asymmetric divisions are crucial for generating cell diversity;they rely on coupling between polarity cues and spindle positioning,but how this coupling is achieved is poorly understood. In one-cellstage Caenorhabditis elegans embryos, polarity cues set by thePAR proteins mediate asymmetric spindle positioning by governingan imbalance of net pulling forces acting on spindle poles.We found that the GoLoco-containing proteins GPR-1 and GPR-2,as well as the G subunits GOA-1 and GPA-16, were essential forgeneration of proper pulling forces. GPR-1/2 interacted withguanosine diphosphate-bound GOA-1 and were enriched on the posteriorcortex in a par-3 and par-2dependent manner. Thus,the extent of net pulling forces may depend on cortical G activity,which is regulated by anterior-posterior polarity cues throughGPR-1/2.
1 Swiss Institute for Experimental Cancer Research (ISREC), 1066 Epalinges/Lausanne, Switzerland. 2 Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany. 3 Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
* To whom correspondence should be addressed. E-mail: pierre.gonczy{at}isrec.unil.ch
Structural Determinants Underlying the Temperature-sensitive Nature of a G{alpha} Mutant in Asymmetric Cell Division of Caenorhabditis elegans.
C. A. Johnston, K. Afshar, J. T. Snyder, G. G. Tall, P. Gonczy, D. P. Siderovski, and F. S. Willard (2008)
J. Biol. Chem.
283, 21550-21558
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Interphase microtubule bundles use global cell shape to guide spindle alignment in fission yeast.
A default mechanism of spindle orientation based on cell shape is sufficient to generate cell fate diversity in polarised Xenopus blastomeres.
B. Strauss, R. J. Adams, and N. Papalopulu (2006)
Development
133, 3883-3893
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Identification of a receptor-independent activator of G protein signaling (AGS8) in ischemic heart and its interaction with Gbeta{gamma}.
M. Sato, M. J. Cismowski, E. Toyota, A. V. Smrcka, P. A. Lucchesi, W. M. Chilian, and S. M. Lanier (2006)
PNAS
103, 797-802
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Cortical localization of the G{alpha} protein GPA-16 requires RIC-8 function during C. elegans asymmetric cell division.
K. Afshar, F. S. Willard, K. Colombo, D. P. Siderovski, and P. Gonczy (2005)
Development
132, 4449-4459
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Locomotion defects, together with Pins, regulates heterotrimeric G-protein signaling during Drosophila neuroblast asymmetric divisions.
F. Yu, H. Wang, H. Qian, R. Kaushik, M. Bownes, X. Yang, and W. Chia (2005)
Genes & Dev.
19, 1341-1353
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Cleavage furrow formation and ingression during animal cytokinesis: a microtubule legacy.
P. P. D'Avino, M. S. Savoian, and D. M. Glover (2005)
J. Cell Sci.
118, 1549-1558
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The RGS14 GoLoco Domain Discriminates among G{alpha}i Isoforms.
The forces that position a mitotic spindle asymmetrically are tethered until after the time of spindle assembly.
J.-C. Labbe, E. K. McCarthy, and B. Goldstein (2004)
J. Cell Biol.
167, 245-256
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Identification and Characterization of AGS4: A PROTEIN CONTAINING THREE G-PROTEIN REGULATORY MOTIFS THAT REGULATE THE ACTIVATION STATE OF Gi{alpha}.
X. Cao, M. J. Cismowski, M. Sato, J. B. Blumer, and S. M. Lanier (2004)
J. Biol. Chem.
279, 27567-27574
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AGS3 and Signal Integration by G{alpha}s- and G{alpha}i-coupled Receptors: AGS3 BLOCKS THE SENSITIZATION OF ADENYLYL CYCLASE FOLLOWING PROLONGED STIMULATION OF A G{alpha}i-COUPLED RECEPTOR BY INFLUENCING PROCESSING OF G{alpha}i.
M. Sato, T. W. Gettys, and S. M. Lanier (2004)
J. Biol. Chem.
279, 13375-13382
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Thermodynamic Characterization of the Binding of Activator of G Protein Signaling 3 (AGS3) and Peptides Derived from AGS3 with G{alpha}i1.