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A complex of LIN-5 and GPR proteins regulates G protein signaling and spindle function in C. elegans
Open accessAbstract
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 p rotein r egulator), 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 Gα i/o . Inactivation of lin-5 , gpr-1/gpr-2 , or the Gα 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/Gα 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 Gα i/o signaling.
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Cites
Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
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Receptor-independent Activators of Heterotrimeric G-protein Signaling Pathways
Takesono, A., Cismowski, M. J., Ribas, C., Bernard, M., Chung, P., Hazard, S., Duzic, E., & Lanier, S. M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.47.33202 · Cited by 274
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Lechler, T., & Fuchs, E. (2005) · Nature · doi:10.1038/nature03922 · Cited by 998
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Syrovatkina, V., Alegre, K. O., Dey, R., & Huang, X.-Y. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.08.002 · Cited by 498
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Betschinger, J., & Knoblich, J. A. (2004) · Current Biology · doi:10.1016/j.cub.2004.08.017 · Cited by 448
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Morin, X., & Bellaïche, Y. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.06.012 · Cited by 423
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Du, Q., & Macara, I. G. (2004) · Cell · doi:10.1016/j.cell.2004.10.028 · Cited by 369
Metadata
- Authors
- Srinivasan, D. G., Fisk, R. M., Xu, H., & van den Heuvel, S.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2003-05-02
- Volume
- 17
- Issue
- 10
- Pages
- 1225-1239
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2026060763
- Cited by
- 231
- References
- 3
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Srinivasan, D. G., Fisk, R. M., Xu, H., & van den Heuvel, S. (2003). A complex of LIN-5 and GPR proteins regulates G protein signaling and spindle function in C. elegans. Genes & Development. https://doi.org/10.1101/gad.1081203
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