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Signal Transduction by VIP and PACAP Receptors

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dc.abstract.enHomeostasis of the human immune system is regulated by many cellular components, including two neuropeptides, VIP and PACAP, primary stimuli for three class B G protein-coupled receptors, VPAC1, VPAC2, and PAC1. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) regulate intestinal motility and secretion and influence the functioning of the endocrine and immune systems. Inhibition of VIP and PACAP receptors is an emerging concept for new pharmacotherapies for chronic inflammation and cancer, while activation of their receptors provides neuroprotection. A small number of known active compounds for these receptors still impose limitations on their use in therapeutics. Recent cryo-EM structures of VPAC1 and PAC1 receptors in their agonist-bound active state have provided insights regarding their mechanism of activation. Here, we describe major molecular switches of VPAC1, VPAC2, and PAC1 that may act as triggers for receptor activation and compare them with similar non-covalent interactions changing upon activation that were observed for other GPCRs. Interhelical interactions in VIP and PACAP receptors that are important for agonist binding and/or activation provide a molecular basis for the design of novel selective drugs demonstrating anti-inflammatory, anti-cancer, and neuroprotective effects. The impact of genetic variants of VIP, PACAP, and their receptors on signalling mediated by endogenous agonists is also described. This sequence diversity resulting from gene splicing has a significant impact on agonist selectivity and potency as well as on the signalling properties of VIP and PACAP receptors.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorLatek, Dorota
dc.contributor.authorSanmukh, Swapnil
dc.contributor.authorCouvineau, Alain
dc.contributor.authorJeandriens, Jérôme
dc.contributor.authorLanger, Ingrid
dc.date.accessioned2024-01-26T07:36:27Z
dc.date.available2024-01-26T07:36:27Z
dc.date.copyright2022-02-09
dc.date.issued2022
dc.description.accesstimeAT_PUBLICATION
dc.description.financeŚrodki finansowe, o których mowa w art. 365 pkt. 2 ustawy
dc.description.number2
dc.description.sdgGoodHealthAndWellBeing
dc.description.versionFINAL_PUBLISHED
dc.description.volume10
dc.identifier.doi10.3390/BIOMEDICINES10020406
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/119791
dc.identifier.weblinkhttps://www.mdpi.com/2227-9059/10/2/406/pdf
dc.languageeng
dc.pbn.affiliationbiological sciences
dc.relation.ispartofBiomedicines
dc.relation.pages406
dc.rightsCC-BY
dc.sciencecloudnosend
dc.subject.enClass B
dc.subject.enG protein-coupled receptors
dc.subject.enGene co-occurrence
dc.subject.enMicroswitches
dc.subject.enNeuropeptides
dc.subject.enPAC1
dc.subject.enPituitary adenylate cyclase activating polypeptide
dc.subject.enReceptor activation
dc.subject.enSecretin-like GPCRs
dc.subject.enSequence conservation
dc.subject.enSplice variants
dc.subject.enSplicing
dc.subject.enVasoactive intestinal polypeptide
dc.subject.enVPAC1
dc.subject.enVPAC2
dc.titleSignal Transduction by VIP and PACAP Receptors
dc.typeJournalArticle
dspace.entity.typePublication