A complex of LIN-5 and GPR proteins regulates G protein signaling and spindle function in C. elegans

  1. Dayalan G. Srinivasan1,
  2. Ridgely M. Fisk1,
  3. Huihong Xu, and
  4. Sander van den Heuvel2
  1. Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, USA

Abstract

The Caenorhabditis elegans coiled-coil protein LIN-5 mediates several processes in cell division that depend on spindle forces, including alignment and segregation of chromosomes and positioning of the spindle. Here, we describe two closely related proteins, GPR-1 and GPR-2 (G proteinregulator), which associate with LIN-5 in vivo and in vitro and depend on LIN-5 for localization to the spindle and cell cortex. GPR-1/GPR-2 contain a GoLoco/GPR motif that mediates interaction with GDP-bound Gαi/o. Inactivation of lin-5,gpr-1/gpr-2, or the Gαi/o genes goa-1 andgpa-16 all cause highly similar chromosome segregation and spindle positioning defects, indicating a positive role for the LIN-5 and GPR proteins in G protein signaling. The lin-5 andgpr-1/gpr-2 genes appear to act downstream of the parpolarity genes in the one- and two-cell stages and downstream of the tyrosine kinase-related genes mes-1 and src-1 at the four-cell stage. Together, these results indicate that GPR-1/GPR-2 in association with LIN-5 activate G protein signaling to affect spindle force. Polarity determinants may regulate LIN-5/GPR/Gα locally to create the asymmetric forces that drive spindle movement. Results inC. elegans and other species are consistent with a novel model for receptor-independent activation of Gαi/o signaling.

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Footnotes

  • 1 These authors contributed equally to this work.

  • 2 Corresponding author.

  • E-MAIL heuvel{at}helix.mgh.harvard.edu; FAX (617) 724-9648.

  • Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1081203.

    • Received February 7, 2003.
    • Accepted March 18, 2003.
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