Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-10-13
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0092-8674
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
119
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
219-30
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15479639-Animals, pubmed-meshheading:15479639-Caenorhabditis elegans, pubmed-meshheading:15479639-Caenorhabditis elegans Proteins, pubmed-meshheading:15479639-Cell Division, pubmed-meshheading:15479639-Embryo, Nonmammalian, pubmed-meshheading:15479639-Enzyme Activation, pubmed-meshheading:15479639-Epistasis, Genetic, pubmed-meshheading:15479639-GTP-Binding Protein alpha Subunits, pubmed-meshheading:15479639-Guanine Nucleotide Dissociation Inhibitors, pubmed-meshheading:15479639-Guanine Nucleotide Exchange Factors, pubmed-meshheading:15479639-Microtubules, pubmed-meshheading:15479639-Mitotic Spindle Apparatus, pubmed-meshheading:15479639-Nuclear Proteins, pubmed-meshheading:15479639-Protein Binding, pubmed-meshheading:15479639-RNA Interference, pubmed-meshheading:15479639-Stress, Mechanical, pubmed-meshheading:15479639-Two-Hybrid System Techniques
pubmed:year
2004
pubmed:articleTitle
RIC-8 is required for GPR-1/2-dependent Galpha function during asymmetric division of C. elegans embryos.
pubmed:affiliation
Swiss Institute for Experimental Cancer Research (ISREC), 1066 Epalinges/Lausanne, Switzerland.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't