RIC-8 is required for GPR-1/2-dependent Gα function during asymmetric division of C. elegans embryos

Katayoun Afshar, Francis S. Willard, Kelly Colombo, Christopher A. Johnston, Christopher R. McCudden, David P. Siderovski, Pierre Gönczy

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

Heterotrimeric G proteins are crucial for asymmetric cell division, but the mechanisms of signal activation remain poorly understood. Here, we establish that the evolutionarily conserved protein RIC-8 is required for proper asymmetric division of one-cell stage C. elegans embryos. Spindle severing experiments demonstrate that RIC-8 is required for generation of substantial pulling forces on astral microtubules. RIC-8 physically interacts with GOA-1 and GPA-16, two Gα subunits that act in a partially redundant manner in one-cell stage embryos. RIC-8 preferentially binds to GDP bound GOA-1 and is a guanine nucleotide exchange factor (GEF) for GOA-1. Our analysis suggests that RIC-8 acts before the GoLoco protein GPR-1/2 in the sequence of events leading to Gα activation. Furthermore, coimmunoprecipitation and in vivo epistasis demonstrate that inactivation of the Gβ subunit GPB-1 alleviates the need for RIC-8 in one-cell stage embryos. Our findings suggest a mechanism in which RIC-8 favors generation of Gα free from Gβγ and enables GPR-1/2 to mediate asymmetric cell division.

Original languageEnglish
Pages (from-to)219-230
Number of pages12
JournalCell
Volume119
Issue number2
DOIs
StatePublished - 15 Oct 2004

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    Afshar, K., Willard, F. S., Colombo, K., Johnston, C. A., McCudden, C. R., Siderovski, D. P., & Gönczy, P. (2004). RIC-8 is required for GPR-1/2-dependent Gα function during asymmetric division of C. elegans embryos. Cell, 119(2), 219-230. https://doi.org/10.1016/j.cell.2004.09.026