Extracellular signal-regulated kinases – a potential pathway for GPCR-targeted drug discovery Nicola J Smith, Lauren T May, and Natasha L Grimsey for their work on Highlights and hot topics in GPCR research from 'Down Let’s dive into the Classified GPCR News from May 20th to 26th, 2024. receptor in intestinal stem cells to exacerbate colitis The EBI2 receptor is coexpressed with CCR5 in CD4+ T

Recent studies in experimental animals have shown that certain subsets of T cells express functional In contrast, less is known about the expression and function of the GLP-1R in human T cells. Here, we provide evidence that activated human T cells express GLP-1R. Analysis of CD4+ T cells activated under T helper (Th) 1, Th2, Th17 and regulatory T (Treg) cell differentiation GLP-1R in human CD4+ T cells.

October 2022 GPR15 expressed in T lymphocytes from RA patients is involved in leukocyte chemotaxis to Recent evidence indicates that GPR15 may be associated with modulation of the chronic inflammatory response of synovial fluid and peripheral blood were analyzed for CD45+CD3+CD4+GPR15+ and CD45+CD3+CD8+GPR15+ T Statistical analysis included Kruskal-Wallis test, T-test, or Mann-Whitney U test, according to data Also, the frequency CD4+/CD8+ GPR15+ T lymphocytes are higher in synovial fluid of established RA patients

Welcome to the 4th official Adhesion GPCR Consortium newsletter! We welcome suggestions, feedback, and announcements from the community. Announcements Please save the date for the 2024 aGPCR workshop hosted by Antony Boucard! This exciting conference will take place from October 23-25th. We'll see you in Mexico City! Please see this website for details on the conference and the Logo Contest! Member Profile Antony Boucard Professor Centro de Investigación y de Estudios Avanzados del IPN (Cinvestav) How did you become involved in adhesion GPCR research? What is your backstory? AB: I became aware of the existence of adhesion GPCRs while completing my graduate studies. The family of adhesion GPCRs called the Latrophilins or ADGRLs first captured my attention due to their involvement in neuronal synapses uncovered through the mechanism of action of a paralyzing component from black spider venom. For my postdoctoral training, I joined one of the labs that participated in Latrophilins’ discovery, the lab of Dr. Thomas Südhof, but did not start working on them right away. This was because, at that time, the neurexins, another family of adhesion molecules that also happened to be targeted by the same spider toxin as latrophilins, were a more pressing matter. Transitioning to study Latrophilins, I decided to test the interaction of neurexins with Latrophilins. To my surprise and delight, the neurexins happened to be ligands for one isoform of the Latrophilins. Another chapter was being written for me and has been in full redaction since then. What do you think is the next great hurdle in the aGPCR field? What challenges will researchers overcome in the next 10 years? AB: One of the big challenges that the field will have to face in the next 10 years is deciphering the physiological relevance of splice-dependent aGPCR diversity. Alternative splicing events account for hundreds, if not thousands, of potentially divergent isoforms throughout many species. The distribution, functionality, and structure of the multiple splice isoforms that adhesion GPCRs possess are currently unknown. This will greatly impact not only the way we understand how aGPCR works but might also provide a guide to how pharmacological approaches will be developed, i.e., splice isoform-specific agonist/antagonist compounds. How did you become involved with the AGC? Who volunteered you to host the next workshop? AB: I became involved with the AGC through a suggestion from one of my colleagues to join this select group, which was getting together to talk about my favorite molecules. If I wanted to be part of the narrative, I felt that I had to join the community. And so I did. My first meeting was in Boston. I still remember entering the Hall at Boston ́s Children Hospital, going to register and being asked who was my PI. As much as I was shocked that I wasn’t asked if I was a student or a PI, I was more proud to say that I was coming as the founder of my own lab. I was volunteered to host the AGC Workshop by two Board members, Tobias Langenhan and Jörg Hamann. I said yes as soon as they approached me. I, in turn, recruited Yamina Berchiche, founder of DrGPCR.com, to join me in this endeavor. What are you most excited about for the upcoming workshop? If someone is flying in from the other side of the globe, what are three things they must experience in Mexico City? AB: The next workshop will likely bring together some of the hottest adhesion GPCR research going on right now and set the tone for the upcoming years. The excitement I felt when I first attended back in Boston is the same one I feel now that I am the organizer. Also, seeing the expanding diversity among the aGPCR community, added to the fact that this will all take place for the first time in a developing country like Mexico, is paramount. There are a lot of firsts in this perspective: the first time in a LATAM country, the first organized by Afro-descendants (Yamina Berchiche, my co-organizer, has African roots, and my origins are Afro-Carribean). This might not be a big deal for many, but in this new era of making sure that historically excluded demographics are finally included, this represents a building block to reinforce the need for diversity in science. A small step toward leveling the playing field. When in Mexico City from 23-25 October, here is my bucket list of the 3 things that people should absolutely experience: The Day of the Dead celebrations: This happens over the weekend during the end of October and takes the shape of costume parades in which everybody contributes their own versions of the Catarinas (Folklore Mexican ghost lady) or explores the mysterious world of the Alebrijes. Of course, there is the famous parade popularized by the James Bond movie Spectre. The food: While in Mexico, eat like one. The diversity is humongous. No wonder why Mexican cuisine has obtained the coveted status of UNESCO ́s Intangible Cultural Heritage of Humanity. The Teotihuacan Pyramids: although it is very touristy, it is just a hop away from Mexico City and finds its way on many destination lists for a reason. A reminder of how fragile civilizations can be. What is your favorite taco? What mariachi song are you most likely to shout along to at 3 AM? AB: Favorite Taco: Taco de suadero (pronounced swa-day-ro), fatty, with meat caramelized in its own fat, tender, and—oh, did I say fatty? Note that Taco al Pastor is a staple among Mexico City’s delicious tacos. The meat on a rotating spit with its bright red/orange chili-based marinade (spicy but not hot) catches your eye. The way it is served with swiftly chopped charred pineapple for garnish adds to the visuals. A must-try! Mariachi song: I typically do not sing to these since they are dear to Mexican childhood memories, and I feel like an imposter if I do. However, Reggaetón is a highly dynamic genre that attracts many here in Mexico, not to forget salsa music. Don’t be surprised if you find yourself singing Daddy Yankee’s “Gasolina” from the top of your lungs while executing your best perreo or Luis Enrique’s “Yo no sé mañana” while a stranger takes you floating across the dance floor. If this is not the case, go to another party. I know I have. New Insights Members Torsten Schöneberg and Ines Liebscher present an interactive browser-based application, Splice-O-Mat, for understanding tissue distribution of alternatively spliced genes. PMID 38421639 Systematic assessment of the tethered agonist-dependent activities of all 33 aGPCRs in a suite of transcriptional reporter, G protein activation and B-arrestin recruitment assays. PMID: 38608683 The activation profile of different G proteins by ADGRL3 is shown using a collection of biosensor constructs. PMID: 38412860 GPR133 is hypomethylated and upregulated in decidual macrophages in recurrent spontaneous miscarriage patients. PMID: 38564758 BAI1 is expressed in the afferent spiral ganglion neurons in the mouse cochlea where it localizes AMPA receptors at the post-synaptic density and plays a crucial role in sound transmission. PMID: 38564333 CD97 expression is upregulated upon orthodontic compression and inhibits osteoclast differentiation, likely by Rap1a/ERK signaling pathway. PMID: 38311610 Member Dimitris Placantonakis’s identifies extended synaptotagmin 1 as an intracellular interaction partner of GPR133 using proximity labeling. PMID: 38758649 Member Simone Prömel’s lab shows that the nematode (C. elegans) homolog of CELSR, FMI-1, modulates the composition of the ECM and nematode body size. PMID: 38378098 Curated by Sumit J. Bandekar with help from Nathan Zaidman and Abhishek K. Singh

Naveen Thakur, Kenneth A Jacobson, Matthew T Eddy, et al. for their analysis on Membrane mimetic-dependence Let’s dive into the Classified GPCR News from April 29th to May 12th, 2024 Adhesion GPCRs Essential Role being one of the first AI companies out front and to go public GPCR Events, Meetings, and Webinars May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS

Let’s dive into the Classified GPCR News from May 13th to 19th, 2024. 𝐀𝐋𝐋𝐎𝐃𝐃: 𝐀𝐥𝐥𝐨𝐬𝐭𝐞𝐫𝐲 𝐢𝐧 𝐃𝐫𝐮𝐠 𝐃𝐢𝐬𝐜𝐨𝐯𝐞𝐫𝐲 GPCR Events, Meetings, and Webinars May

Divergent roles for the gut intraepithelial lymphocyte GLP-1R in control of metabolism, microbiota, and T anti-inflammatory actions of GLP-1RAs require the gut IEL GLP-1R to selectively restrain local and systemic T effects are mediated by the suppression of gut IEL effector functions linked to the dampening of proximal T

Let’s dive into the Classified GPCR News from May 27th to June 2nd, 2024.

Hello readers! We got a little busy with all the major events at Dr.GPCR, so our weekly news looks slightly different. We will be back next week with our regular weekly GPCR news digest. In the meantime, you can always check the  Classified GPCR News from the last weeks. Today, we celebrate a huge milestone by releasing Episode #150 of the Dr. GPCR Podcast. Join us in this wonderful episode to meet the team of volunteers behind the work you see. The story behind how Dr.GPCR came to be, the people behind the process, the great anecdotes, and what’s coming next. We also have some important announcements in today’s episode, so join us in this celebration and be the first to know about all the changes coming to Dr. GPCR. Today is also the first session of our hands-on workshop with Dr. Sam Hoare. If you aren't joining us this time, stay tuned for more Dr. GPCR University content coming soon.

Below is your Classified GPCR News at a glance for May 22 to 28, 2023.

Below is your Classified GPCR News at a glance for May 15th to 21st, 2023. (May 22 - 26, 2023) 2nd LEAPS Meets Life Sciences Conference. (May 14 - 19, 2023) PEGS Boston (May 15 - 19, 2023) 8th and final ERNEST Meeting in Crete. (May 3 - 7, 2023). The Illuminating the Understudied Druggable Proteome Conference.

Remember to join us tomorrow, May 19th, for the highly anticipated Dr. Below is your Classified GPCR News at a glance for May 8th to 14th, 2023. (May 22 - 26, 2023) 2nd LEAPS Meets Life Sciences Conference. (May 14 - 19, 2023) PEGS Boston (May 15 - 19, 2023) 8th and final ERNEST Meeting in Crete. (May 3 - 7, 2023). The Illuminating the Understudied Druggable Proteome Conference.

Save the date and join us next week, May 19th, 2023 for the Dr. Below is your Classified GPCR News at a glance for May 1 to 7, 2023. (May 22 - 26, 2023) 2nd LEAPS Meets Life Sciences Conference. (May 14 - 19, 2023) PEGS Boston (May 15 - 19, 2023) 8th and final ERNEST Meeting in Crete. (May 3 - 7, 2023). The Illuminating the Understudied Druggable Proteome Conference.

Below is your Classified GPCR News at a glance for May 29th to June 4th, 2023.

April 2022 John Streicher talks about his work on terpenes found in cannabis as these may be a novel These compounds may be a novel way to treat pain without the negative side effects of cannabinoids or

Targeted mutagenesis may miss broader functional regions, while random mutagenesis generates extensive T., Baltos, J.-A., Thomas, T., Nguyen, T. D., Muñoz, L. L., Gregory, K. J., White, P. M., Christopoulos, A., & May, L. T. (2016).

For example, the lipid composition of intracellular membranes may influence GPCR dynamics and signaling These compartments have distinct biochemical environments, which may affect the stability and functionality This may involve the development of specialized delivery vehicles, such as nanoparticles or liposomes Tagging molecules may alter the conformation or activity of GPCRs, leading to unintended effects on downstream T., Gardella, T. J., & Vilardaga, J. P. (2009).

and scavenging (Volpe S. et al., 2012), which molecular signature was recently characterized (Shroka, T. T., et al., 2013). migrate by remaining responsive to chemokines, it dampens the inflammatory response when needed; and it may J., et al. 2010), which may ultimately compete with receptor antagonists, thereby decreasing the efficacy and the pathological consequences that may arise from its disruption.

September 2022 "T cells are master regulators of the immune response tuning, among others, B cells, macrophages To exert their functions requiring high sensibility and specificity, T cells need to integrate different role of the cytoskeleton and lipid microdomains in controlling signalling compartmentalization during T Here, we discuss mechanisms responsible for signalling amplification and compartmentalization in T cell mutations carried by distinct signalling proteins giving rise to syndromes characterized by defects in T

Stuart Maudsley, Nicole Perry-Hauser, Lauren Slosky, Cesare Orlandi, and Simone Prömel. GPCR University Save the date for our upcoming workshop starting May 9th, 2024, featuring Dr. Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS

Lauren Slosky, Dr. Christel Menet, Dr. Ben Myers and Dr. Niña Caculitan. sorafenib added to cladribine, high-dose cytarabine, G-CSF, and mitoxantrone in untreated AML miR-19a may 2024 | Ligand Recognition and Molecular Gating Conference April 5 - 10, 2024 | AACR Annual Meeting May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS

their AlphaFold2 predicted water-soluble QTY variants and uncovering the natural mutations of L->Q, I->T, F->Y and Q->L, T->I and Y->F Industry News Sosei Heptares Doses First Subject in Phase 1 Trial with Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS

SNARE protein found on the synaptic vesicle membrane in neurons and is responsible for binding to the t-SNARE The t-SNARE complex is composed of two different proteins: syntaxin and SNAP-25; syntaxin is found on The t-SNARE complex and VAMP2 interact to form the SNARE complex, which is essential for the fusion of Some studies have suggested that VAMP2 may be involved in regulating dopamine D2 receptor signaling by

GPCRs in Oncology and Immunology The GPCR-Gαs-PKA signaling axis promotes T cell dysfunction and cancer receptors induces IFN-γ but suppresses IL-2 production by inhibiting activation of pAKT pathways in primary T Oncology Confo Therapeutics and AbCellera partner on GPCR-targeting antibodies GPCR Inhibition With ICB May

RGS4 is expressed in various immune cells, including T cells and B cells, and has been shown to modulate RGS4 acts as a negative regulator of T cell activation, and its expression is upregulated in response to T cell activation[6]. Wang, D., The essential role of G protein-coupled receptor (GPCR) signaling in regulating T cell immunity Avrampou, K., et al., RGS4 Maintains Chronic Pain Symptoms in Rodent Models.

Matthew T Eddy and his team's research on A2A adenosine receptor activation by G protein and mutations Or maybe looking for your next opportunity? The combination of brentuximab vedotin and chidamide synergistically suppresses the proliferation of T-cell Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting April 22 - 23, 2024 | Endocrine Metabolic GPCRs May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS

Oliver Hartley, was at the PEGS Europe Novartis pays Legend $100M upfront to give solid tumor CAR-T the T-Charge treatment Innovation And Healthcare Meet At Novartis Neurocrine Biosciences Announces Settlement Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting April 22 - 23, 2024 | Endocrine Metabolic GPCRs May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS

This emphasis may have caused other signaling pathways to be overlooked due to a need for adequate assay ERK activation pathways can be categorised into two main sub-pathways based on their subcellular localisation Kenakin, T. (2019). Biased receptor signaling in drug discovery. Sugiura, R., Satoh, R., & Takasaki, T. (2021). ERK: a double-edged sword in cancer.