Ask about this productRelated genes to: RIC8B Blocking Peptide
- Gene:
- RIC8B NIH gene
- Name:
- RIC8 guanine nucleotide exchange factor B
- Previous symbol:
- -
- Synonyms:
- FLJ10620, hSyn, RIC8
- Chromosome:
- 12q23.3
- Locus Type:
- gene with protein product
- Date approved:
- 2005-08-17
- Date modifiied:
- 2014-11-18
Related products to: RIC8B Blocking Peptide
Related articles to: RIC8B Blocking Peptide
- Primary cilia exhibit conserved organization and contain structural and functional domains of unique molecular composition. The inversin compartment (InvC), which is found in the proximal ciliary segment of a subset of vertebrate and invertebrate cell types, concentrates different classes of signaling molecules. Mutations in genes encoding resident proteins of the InvC manifest in ciliopathies, highlighting the importance of the InvC in cilia biology. We previously showed that a chaperone of Gα proteins RIC-8 localizes to the InvC of channel cilia; however, the mechanisms that regulate RIC-8 targeting to this ciliary sub-domain or RIC-8 function in the InvC remain unknown. Here, we build on our prior work to demonstrate that RIC-8 becomes restricted to the InvC during larval development and show that, while the RVxP motif and intact transition zone are required for its proper intraciliary distribution, RIC-8 localization to the cilium depends on intraflagellar transport. Using the ASH neuron as a model, we establish that RIC-8 functions in channel cilia to modulate chemosensory responses. Finally, we demonstrate that human RIC8A and RIC8B proteins are required for ciliogenesis in RPE-1 cells. Collectively, our results define ciliary trafficking mechanisms and novel cell-specific functions for a highly conserved signaling protein. - Source: PubMed
Publication date: 2026/02/09
Campagna ChristinaDescoteaux Abigail EPool AbigailPeet EricMalaiwong NawaphatO'Donnell Michael PNechipurenko Inna - Resistance to inhibitors of cholinesterase 8B (RIC8B) functions as a chaperone and guanine nucleotide exchange factor for Gαs/olf. We focused on RIC8B variant 1 (v1), which is abundantly expressed at the mRNA level, and variant 4 (v4), which lacks the C-terminal cradle loop helix (CLH) domain. Together with 3 closely related variants (v2, v3, and v10), we evaluated 5 variants for chaperone activity. HEK293T cells were co-expressed with olfactory receptors (ORs), and odorant-induced cAMP production was used as a functional readout. Among the variants tested, only v4 consistently suppressed cAMP responses. AlphaFold3-based complex structure prediction indicated that v1 forms multiple hydrogen bonds with Gαs via its CLH domain, whereas v4 failed to establish these interactions. This suggests that v4 may be unable to stably adopt the proper binding conformation with Gαs, potentially resulting in improperly folded Gαs that exert a dominant-negative effect on OR responses. - Source: PubMed
Shirai RinaHinuma ShujiKuroda Shun'ichi - Resistance to inhibitors of cholinesterases (ric-8 proteins) are involved in modulating G-protein function, but little is known of their potential physiological importance in the heart. In the present study, we assessed the role of resistance to inhibitors of cholinesterase 8b (Ric-8b) in determining cardiac contractile function. We developed a murine model in which it was possible to conditionally delete ric-8b in cardiac tissue in the adult animal after the addition of tamoxifen. Deletion of ric-8b led to severely reduced contractility as measured using echocardiography days after administration of tamoxifen. Histological analysis of the ventricular tissue showed highly variable myocyte size, prominent fibrosis, and an increase in cellular apoptosis. RNA sequencing revealed transcriptional remodeling in response to cardiac ric-8b deletion involving the extracellular matrix and inflammation. Phosphoproteomic analysis revealed substantial downregulation of phosphopeptides related to myosin light chain 2. At the cellular level, the deletion of ric-8b led to loss of activation of the L-type calcium channel through the β-adrenergic pathways. Using fluorescence resonance energy transfer-based assays, we showed ric-8b protein selectively interacts with the stimulatory G-protein, Gαs. We explored if deletion of Gnas (the gene encoding Gα) in cardiac tissue using a similar approach in the mouse led to an equivalent phenotype. The conditional deletion of the Gα gene in the ventricle led to comparable effects on contractile function and cardiac histology. We conclude that ric-8b is essential to preserve cardiac contractile function likely through an interaction with the stimulatory G-protein and downstream phosphorylation of myosin light chain 2. - Source: PubMed
Publication date: 2024/06/13
Tsisanova ElenaNobles MurielSebastian SoniaNg Keat-EngThomas AlisonWeinstein Lee ScottMunroe Patricia BTinker Andrew - GNAO1 mutated in pediatric encephalopathies encodes the major neuronal G protein Gαo. Of the more than 80 pathogenic mutations, most are single amino acid substitutions spreading across the Gαo sequence. We performed extensive characterization of Gαo mutants, showing abnormal GTP uptake and hydrolysis and deficiencies in binding Gβγ and RGS19. Plasma membrane localization of Gαo was decreased for a subset of mutations that leads to epilepsy; dominant interactions with GPCRs also emerged for the more severe mutants. Pathogenic mutants massively gained interaction with Ric8A and, surprisingly, Ric8B proteins, relocalizing them from cytoplasm to Golgi. Of these 2 mandatory Gα-subunit chaperones, Ric8A is normally responsible for the Gαi/Gαo, Gαq, and Gα12/Gα13 subfamilies, and Ric8B solely responsible for Gαs/Gαolf. Ric8 mediates the disease dominance when engaging in neomorphic interactions with pathogenic Gαo through imbalance of the neuronal G protein signaling networks. As the strength of Gαo-Ric8B interactions correlates with disease severity, our study further identifies an efficient biomarker and predictor for clinical manifestations in GNAO1 encephalopathies. Our work uncovers the neomorphic molecular mechanism of mutations underlying pediatric encephalopathies and offers insights into other maladies caused by G protein malfunctioning and further genetic diseases. - Source: PubMed
Publication date: 2024/06/14
Solis Gonzalo PKoval AlexeyValnohova JanaKazemzadeh ArghavanSavitsky MikhailKatanaev Vladimir L - Alpaca (Vicugna pacos), llama (Lama glama), vicugna (Vicugna vicugna) and guanaco (Lama guanicoe), are the camelid species distributed over the Andean high-altitude grasslands, the Altiplano, and the Patagonian arid steppes. Despite the wide interest on these animals, most of the loci under selection are still unknown. Using whole-genome sequencing (WGS) data we investigated the occurrence and the distribution of Runs Of Homozygosity (ROHs) across the South American Camelids (SACs) genome to identify the genetic relationship between the four species and the potential signatures of selection. - Source: PubMed
Publication date: 2023/08/21
Pallotti StefanoPicciolini MatteoAntonini MarcoRenieri CarloNapolioni Valerio