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Deficiency of β-arrestin2 alleviates apoptosis through GRP78-ATF6-CHOP signaling pathway in primary Sjögren's syndrome The etiology of primary Sjögren's syndrome (pSS) remains unknown, and there is no ideal drug for the specific treatment of pSS. β-arrestin2 is a key protein that mediates desensitization and internalization of G protein-coupled receptors (GPCRs) and it participates in inflammatory and immune responses that have been found to mediate apoptosis in autoimmune disease. In this study, we established an experimental Sjögren's syndrome (ESS) mouse model to elucidate the molecular mechanisms of β-arrestin2 in pSS. First, excessive activation of β-arrestin2 and GRP78-ATF6-CHOP apoptosis signaling were detected in specimens from pSS patients. In vivo, we found that inhibition of GRP78-ATF6-CHOP apoptosis signaling improved ESS symptoms, and the targeted deletion of β-arrestin2 significantly increased saliva flow, alleviated salivary gland indices, and improved tissue integrity in the ESS model by downregulating GRP78-ATF6-CHOP apoptosis signaling. In vitro, we used IFNα to stimulate human salivary gland epithelial cells (HSGECs), and the results showed that IFNα activated GRP78-ATF6-CHOP apoptosis signaling, decreased cell viability, and induced apoptosis, which were negatively regulated by the ERS inhibitor 4-PBA. In addition, β-arrestin2 depletion downregulated GRP78-ATF6-CHOP apoptosis signaling to alleviate cell apoptosis, and the effect depended on the interaction between GRP78 and β-arrestin2. In summary, our results suggest that excessive activation of GRP78-ATF6-CHOP apoptosis signaling is involved in the pathogenesis of pSS and that β-arrestin2 encourages inflammation-induced epithelial apoptosis through GRP78-ATF6-CHOP apoptosis signaling. This research further clarified the underlying role of β-arrestin2 and provided an experimental foundation for β-arrestin2 depletion in the treatment of the human autoimmune disorder pSS. Read full article

Come attend this month's virtual café talk to see the awesome work of Dr. Stuart Maudsley on how an aging physiological context affects #GPCR signaling #drgpcr. Register here (FREE) https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #virtualcafe

Episode 53 of the Dr. GPCR podcast is now available! Our guest is Dr. Tim De Groof! It’s not often when you get the best of both worlds - nano-bodies and #GPCRs. Listen where you get your podcasts https://www.ecosystem.drgpcr.com/dr-gpcr-podcast #gpcr #drgpcr #podcast

Bitter taste receptors (TAS2Rs) are a poorly understood subgroup of G protein-coupled receptors (GPCRs). The experimental structure of these receptors has yet to be determined, and key-residues controlling their function remain mostly unknown. We designed an integrative approach to improve comparative modeling of TAS2Rs. Using current knowledge on class A GPCRs and existing experimental data in the literature as constraints, we pinpointed conserved motifs to entirely re-align the amino-acid sequences of TAS2Rs. We constructed accurate homology models of human TAS2Rs. As a test case, we examined the accuracy of the TAS2R16 model with site-directed mutagenesis and in vitro functional assays. This combination of in silico and in vitro results clarifies sequence-function relationships and proposes functional molecular switches that encode agonist sensing and downstream signaling mechanisms within mammalian TAS2Rs sequences. Read full article

Episode 52 of the Dr. GPCR podcast is now available! Our guest is Dr. Ben Myers! From studying sensory #ionchannels to the group leader at the University of Utah investigating Class F #GPCRs in #cancer. Listen nowhere you get your podcasts https://www.ecosystem.drgpcr.com/dr-gpcr-podcast/ #gpcr #drgpcr #podcast

Episode 51 of the Dr. GPCR podcast is now available! Our guest is Dr. Mark Connor! Learn more about #GPCRs and life as an academic wearing different hats. Listen nowhere you get your podcasts. https://www.ecosystem.drgpcr.com/dr-gpcr-podcast/ #gpcr #drgpcr #podcast

Do you have your ticket for the Dr. GPCR Virtual Cafe? Join us for another virtual cafe talk to hear about the amazing work that Dr. Simone Promel / Promel Lab is doing on adhesion #GPCRs. Register here (free): https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #podcast

Don’t miss out on episode 50 of the Dr. GPCR podcast! Give it a listen to hear from Dr. Thomas P. Sakmar on how the molecular studies of rhodopsin paved the way to understanding #GPCRs Be sure to subscribe! https://www.ecosystem.drgpcr.com/dr-gpcr-podcast/ #drgpcr #gpcr #podcast

Join us and learn how to quantify your kinetic GPCR signaling from the expert himself: Dr. Samuel Hoare / Pharmechanics. Get your ticket now! https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #virtualcafe

Be sure to signup for the next Virtual Cafe of Dr. GPCR on the 24th of June! This time, the GPCRdb team ( Dr. David Gloriam , Dr. Albert Kooistra & Gáspár Pándy-Szekeres ) will present and demonstrate the newest resources of the GPCRdb: 1) the new G protein resources and 2) the structural analysis platform. Reserve your spot for free at: https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #GPCR #GPCRs #DrGPCR #GPCRdb #VirtualCafe

Join us for a fantastic introduction to GPCRdb with Dr. David Gloriam and Dr. Albert Kooistra. Register today: https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #virtualcafe

Did you register for our next Dr. GPCR Virtual Cafe? Register today! Addgene's Dr. Joanne Kamens is our guest. If you need a plasmid for your research or you want to share your materials, this is the place to go. https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #virtualcafe #addgene

Join us for the first virtual cafe talk to hear about the amazing work that Dr. Brian Arey is doing. https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #virtualcafe