RIC-8 is required for GPR-1/2-dependent Galpha function during asymmetric division of C. elegans embryos
| Autor: | Afshar, K., Willard, F. S., Colombo, K., Johnston, C. A., McCudden, C. R., Siderovski, D. P., Gönczy, P. |
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| Předmět: |
Nonmammalian/cytology/physiology
Caenorhabditis elegans Proteins/genetics/*metabolism Research Support P.H.S Stress Caenorhabditis elegans/cytology/*physiology Nuclear Proteins/genetics/*metabolism Genetic hemic and lymphatic diseases Two-Hybrid System Techniques Animals Non-U.S. Gov't fungi Guanine Nucleotide Dissociation Inhibitors/genetics/metabolism Embryo Mechanical Cell Division/*physiology Guanine Nucleotide Exchange Factors/genetics/metabolism GTP-Binding Protein alpha Subunits/metabolism Enzyme Activation Microtubules/metabolism Epistasis RNA Interference U.S. Gov't Mitotic Spindle Apparatus/metabolism Protein Binding |
| Popis: | 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 Galpha 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 Galpha activation. Furthermore, coimmunoprecipitation and in vivo epistasis demonstrate that inactivation of the Gbeta 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 Galpha free from Gbetagamma and enables GPR-1/2 to mediate asymmetric cell division. |
| Databáze: | OpenAIRE |
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