TY - JOUR
T1 - RIC-8 is required for GPR-1/2-dependent Gα function during asymmetric division of C. elegans embryos
AU - Afshar, Katayoun
AU - Willard, Francis S.
AU - Colombo, Kelly
AU - Johnston, Christopher A.
AU - McCudden, Christopher R.
AU - Siderovski, David P.
AU - Gönczy, Pierre
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/10/15
Y1 - 2004/10/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=5444260164&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2004.09.026
DO - 10.1016/j.cell.2004.09.026
M3 - Article
C2 - 15479639
AN - SCOPUS:5444260164
VL - 119
SP - 219
EP - 230
JO - Cell
JF - Cell
SN - 0092-8674
IS - 2
ER -