Human brain synembryn interacts with Gsα and Gqα and is translocated to the plasma membrane in response to isoproterenol and carbachol

Klattenhoff, Carla Andrea; Montecino, Martín; Soto, Ximena; Guzmán, Leonardo; Romo, Ximena; García, María de los Ángeles Olivares; Mellström, Britt; Naranjo, José R.; Hinrichs, María Victoria; Olate, Juan

doi:10.1002/jcp.10300

Cited by 61 publications

(61 citation statements)

References 22 publications

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“…between G protein subunits and Ric-8B or Ric-8A have been described (7,11,13,22,33). However, a complete and comparative profile of the interactions between Ric-8BFL, Ric-8B⌬9, and Ric-8A with representatives of all four classes of G␣ subunits or G␤␥ has not been made.…”

Section: Ric-8 and G Protein Interactions-individual Interactionsmentioning

confidence: 99%

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Ric-8B Is a GTP-dependent G Protein αs Guanine Nucleotide Exchange Factor

Chan

Gabay

Wright

et al. 2011

Journal of Biological Chemistry

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ric-8 (resistance to inhibitors of cholinesterase 8) genes have positive roles in variegated G protein signaling pathways, including G␣ q and G␣ s regulation of neurotransmission, G␣ idependent mitotic spindle positioning during (asymmetric) cell division, and G␣ olf -dependent odorant receptor signaling. Mammalian Ric-8 activities are partitioned between two genes, ric-8A and ric-8B. Ric-8A is a guanine nucleotide exchange factor (GEF) for G␣ i /␣ q /␣ 12/13 subunits. Ric-8B potentiated G s signaling presumably as a G␣ s -class GEF activator, but no demonstration has shown Ric-8B GEF activity. Here, two Ric-8B isoforms were purified and found to be G␣ subunit GDP release factor/GEFs. In HeLa cells, full-length Ric-8B (Ric-8BFL) bound endogenously expressed G␣ s and lesser amounts of G␣ q and G␣ 13 . Ric-8BFL stimulated guanosine 5-3-O-(thio)triphosphate (GTP␥S) binding to these subunits and G␣ olf , whereas the Ric-8B⌬9 isoform stimulated G␣ s short GTP␥S binding only. Michaelis-Menten experiments showed that Ric-8BFL elevated the V max of G␣ s steady state GTP hydrolysis and the apparent K m values of GTP binding to G␣ s from ϳ385 nM to an estimated value of ϳ42 M. Directionality of the Ric-8BFL-catalyzed G␣ s exchange reaction was GTP-dependent. At sub-K m GTP, Ric-BFL was inhibitory to exchange despite being a rapid GDP release accelerator. Ric-8BFL binds nucleotide-free G␣ s tightly, and near-K m GTP levels were required to dissociate the Ric-8B⅐G␣ nucleotide-free intermediate to release free Ric-8B and G␣-GTP. Ric-8BFL-catalyzed nucleotide exchange probably proceeds in the forward direction to produce G␣-GTP in cells.Heterotrimeric G proteins transduce signals received from ligand-bound G protein-coupled receptors (GPCRs) 2 to intracellular effector enzymes. Agonist-bound GPCRs activate coupled G protein heterotrimers by accelerating the rate of GDP for GTP exchange on the G␣ subunit (1). The understanding of G protein signaling pathway complexity expanded beyond this traditional paradigm when modulatory proteins that regulate G protein activation apart from receptors were uncovered and characterized (2-7).One well characterized non-receptor G protein activator is Ric-8 (resistance to inhibitors of cholinesterase 8A). ric-8 was first identified in a genetic screen devised to find mutants of genes that positively regulated Caenorhabditis elegans neurotransmission (8). Through genetic epistasis analyses, it was predicted that ric-8 action was elicited upstream of G␣ q and/or G␣ s to regulate divergent G protein signaling outputs (8 -10). Ric-8 was first linked physically to G proteins when two homologous mammalian Ric-8 proteins (so-named Ric-8A and Ric-8B) were isolated in yeast two hybrid screens using G␣ o and G␣ s baits, respectively. Ric-8A interacted with G␣ i/o , G␣ q , and G␣ 13 subunits (7). Ric-8B interacted with G␣ s and G␣ q (7, 11). Evidence of a preferred interaction of Ric-8A with G␣ i -GDP led to experimentation showing that Ric-8A was a guanine nucleotide exchange factor for the monomeric G␣...

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Section: Ric-8 and G Protein Interactions-individual Interactionsmentioning

confidence: 99%

“…Ric-8A interacted with G␣ i/o , G␣ q , and G␣ 13 subunits (7). Ric-8B interacted with G␣ s and G␣ q (7,11). Evidence of a preferred interaction of Ric-8A with G␣ i -GDP led to experimentation showing that Ric-8A was a guanine nucleotide exchange factor for the monomeric G␣ subunits it bound in vitro.…”

mentioning

confidence: 99%

Ric-8B Is a GTP-dependent G Protein αs Guanine Nucleotide Exchange Factor

Chan

Gabay

Wright

et al. 2011

Journal of Biological Chemistry

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“…RIC-8 associates with GDPbound Ga proteins, stimulating the release of GDP and forms a stable nucleotide transition state complex, which is dissociated upon binding of GTP to Ga (Tall et al, 2003). RIC-8 is able to interact with all three major classes of Ga, which are involved in synaptic signaling Klattenhoff et al, 2003;Tall et al, 2003;Couwenbergs et al, 2004). In C. elegans, it participates in the signaling networks, which regulate neurotransmitter release by controlling the production and consumption of diacylglycerol .…”

Section: Introductionmentioning

confidence: 99%

Nucleotide exchange factor RIC‐8 is indispensable in mammalian early development

Tõnissoo¹,

Lulla²,

Meier³

et al. 2010

Developmental Dynamics

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The guanine nucleotide exchange factor RIC-8 is a conserved protein essential for the asymmetric division in the early embryogenesis in different organisms. The function of RIC-8 in mammalian development is not characterized so far. In this study we map the expression of RIC-8 during the early development of mouse. To elucidate the RIC-8 function we used Ric-8 2/2 mutant embryos. The Ric-8 2/2 embryos reach the gastrulation stage but do not develop further and die at E6.5-E8.5. We characterized the Ric-8 2/2 embryonic phenotype by morphological and marker gene analyses. The gastrulation is initiated in Ric-8 2/2 embryos but their growth is retarded, epiblast and mesoderm disorganized. Additionally, the basement membrane is defective, amnion folding and the formation of allantois are interfered, also the cavitation. Furthermore, the orientation of the Ric-8 2/2 embryo in the uterus was abnormal. Our study reveals that the activity of RIC-8 protein is irreplaceable for the correct gastrulation of mouse embryo. Developmental Dynamics 239:3404-3415,

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“…6, which is published as supporting information on the PNAS web site, for these proposed models). Regulation of other G␣ or G␣͞ GoLoco-mediated signaling pathways by Ric-8A is also worth considering, given the number of distinct G␣ binding partners of mammalian Ric-8A and Ric-8B (12,24,25) and the many processes that appear to be regulated by RIC-8 in C. elegans (26)(27)(28).…”

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confidence: 99%

Resistance to inhibitors of cholinesterase 8A catalyzes release of Gαi-GTP and nuclear mitotic apparatus protein (NuMA) from NuMA/LGN/Gαi-GDP complexes

Tall

Gilman

2005

Proc. Natl. Acad. Sci. U.S.A.

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Resistance to inhibitors of cholinesterase (Ric) 8A is a guanine nucleotide exchange factor that activates certain G protein ␣-subunits. Genetic studies in Caenorhabditis elegans and Drosophila melanogaster have placed RIC-8 in a previously uncharacterized G protein signaling pathway that regulates centrosome movements during cell division. Components of this pathway include G protein subunits of the G␣i class, GPR or GoLoco domain-containing proteins, RGS (regulator of G protein signaling) proteins, and accessory factors. These proteins interact to regulate microtubule pulling forces during mitotic movement of chromosomes. It is unclear how the GTP-binding and hydrolysis cycle of G␣i functions in the context of this pathway. In mammals, the GoLoco domain-containing protein LGN (GPSM2), the LGN-and microtubule-binding nuclear mitotic apparatus protein (NuMA), and G␣i regulate a similar process. We find that mammalian Ric-8A dissociates G␣i-GDP͞LGN͞ NuMA complexes catalytically, releasing activated G␣i-GTP in vitro. Ric-8A-stimulated activation of G␣i caused concomitant liberation of NuMA from LGN. We conclude that Ric-8A efficiently utilizes GoLoco͞G␣i-GDP complexes as substrates in vitro and suggest that Ric-8A-stimulated release of G␣i-GTP and͞or NuMA regulates the microtubule pulling forces on centrosomes during cell division.cell division ͉ G protein ͉ GoLoco ͉ GPR ͉ guanine nucleotide exchange

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Human brain synembryn interacts with Gsα and Gqα and is translocated to the plasma membrane in response to isoproterenol and carbachol

Cited by 61 publications

References 22 publications

Ric-8B Is a GTP-dependent G Protein αs Guanine Nucleotide Exchange Factor

Ric-8B Is a GTP-dependent G Protein αs Guanine Nucleotide Exchange Factor

Nucleotide exchange factor RIC‐8 is indispensable in mammalian early development

Resistance to inhibitors of cholinesterase 8A catalyzes release of Gαi-GTP and nuclear mitotic apparatus protein (NuMA) from NuMA/LGN/Gαi-GDP complexes

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