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

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

Afshar, K.  
•
Willard, F. S.
•
Colombo, K.
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2004
Cell

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.

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Type
research article
DOI
10.1016/j.cell.2004.09.026
PubMed ID

15479639

Author(s)
Afshar, K.  
Willard, F. S.
Colombo, K.
Johnston, C. A.
McCudden, C. R.
Siderovski, D. P.
Gönczy, P.  
Date Issued

2004

Published in
Cell
Volume

119

Issue

2

Start page

219

End page

30

Subjects

Animals

•

Caenorhabditis elegans/cytology/*physiology

•

Caenorhabditis elegans Proteins/genetics/*metabolism

•

Cell Division/*physiology

•

*Embryo

•

Nonmammalian/cytology/physiology

•

Enzyme Activation

•

Epistasis

•

Genetic

•

GTP-Binding Protein alpha Subunits/metabolism

•

Guanine Nucleotide Dissociation Inhibitors/genetics/metabolism

•

Guanine Nucleotide Exchange Factors/genetics/metabolism

•

Microtubules/metabolism

•

Mitotic Spindle Apparatus/metabolism

•

Nuclear Proteins/genetics/*metabolism

•

Protein Binding

•

RNA Interference

•

Research Support

•

Non-U.S. Gov't

•

Research Support

•

U.S. Gov't

•

P.H.S.

•

Stress

•

Mechanical

•

Two-Hybrid System Techniques

Note

Swiss Institute for Experimental Cancer Research (ISREC), 1066 Epalinges/Lausanne, Switzerland.

Journal Article

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPGON  
Available on Infoscience
August 24, 2006
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/233786
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