A complex of LIN-5 and GPR proteins regulates G protein signaling and spindle function in C elegans.
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.
Srinivasan
Dayalan G
DG
Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, USA.
Fisk
Ridgely M
RM
Xu
Huihong
H
van den Heuvel
Sander
S
D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D020555:GTP-Binding Protein Regulators / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D013058:Mass Spectrometry; D008941:Spindle Apparatus / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D020555:GTP-Binding Protein Regulators; C404808:lin-5 protein, C elegans; D019204:GTP-Binding Proteins