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Genes & Dev. 17 (10): 1225-1239

Copyright © 2003 by Cold Spring Harbor Laboratory Press.

Vol. 17, No. 10, pp. 1225-1239, May 15, 2003

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

Dayalan G. Srinivasan,1 Ridgely M. Fisk,1 Huihong Xu, and Sander van den Heuvel2

Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, USA

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 protein regulator), 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 Galpha i/o. Inactivation of lin-5, gpr-1/gpr-2, or the Galpha i/o genes goa-1 and gpa-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 and gpr-1/gpr-2 genes appear to act downstream of the par polarity 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/Galpha locally to create the asymmetric forces that drive spindle movement. Results in C. elegans and other species are consistent with a novel model for receptor-independent activation of Galpha i/o signaling.

[Keywords: LIN-5; GoLoco motif; G protein; chromosome segregation; spindle position]

1 These authors contributed equally to this work.

2 Corresponding author.

© 2003 by Cold Spring Harbor Laboratory Press  ISSN 0890-9369/03 $5.00

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