{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:43:08Z","timestamp":1760150588010,"version":"build-2065373602"},"reference-count":60,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,16]],"date-time":"2023-12-16T00:00:00Z","timestamp":1702684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Higher Education Commission","award":["5742","7440"],"award-info":[{"award-number":["5742","7440"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The G protein-coupled \u03b12-adrenoceptor subtype C (abbreviated \u03b12C-AR) has been implicated in peripheral vascular conditions and diseases such as cold feet\u2013hands, Raynaud\u2019s phenomenon, and scleroderma, contributing to morbidity and mortality. Microvascular \u03b12C-adrenoceptors are expressed in specialized smooth muscle cells and mediate constriction under physiological conditions and the occlusion of blood supply involving vasospastic episodes and tissue damage under pathological conditions. A crucial step for receptor biological activity is the cell surface trafficking of intracellular receptors, triggered by cAMP-Epac-Rap1A GTPase signaling, which involves protein\u2013protein association with the actin-binding protein filamin-2, mediated by critical amino acid residues in the last 14 amino acids of the receptor carboxyl (C)-terminus. This study assessed the role of the C-terminus in Rap1A GTPase coupled receptor trafficking by domain-swapping studies using recombinant tagged receptors in transient co-transfections and compared with wild-type receptors using immunofluorescence microscopy. We further tested the biological relevance of the \u03b12C-AR C-terminus, when introduced as competitor peptides, to selectively inhibit intracellular \u03b12C-AR surface translocation in transfected as well as in microvascular smooth muscle cells expressing endogenous receptors. These studies contribute to establishing proof of principle to target intracellular \u03b12C-adrenoceptors to reduce biological activity, which in clinical conditions can be a target for therapy.<\/jats:p>","DOI":"10.3390\/ijms242417558","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T03:59:24Z","timestamp":1702871964000},"page":"17558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibiting Intracellular \u03b12C-Adrenoceptor Surface Translocation Using Decoy Peptides: Identification of an Essential Role of the C-Terminus in Receptor Trafficking"],"prefix":"10.3390","volume":"24","author":[{"given":"Aisha","family":"Raza","sequence":"first","affiliation":[{"name":"Dr. Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1487-3545","authenticated-orcid":false,"given":"Saima","family":"Mohsin","sequence":"additional","affiliation":[{"name":"Dr. Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fasiha","family":"Saeed","sequence":"additional","affiliation":[{"name":"Dr. Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0226-8257","authenticated-orcid":false,"given":"Syed Abid","family":"Ali","sequence":"additional","affiliation":[{"name":"Husein Ebrahim Jamal (H.E.J.) Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7111-828X","authenticated-orcid":false,"given":"Maqsood A.","family":"Chotani","sequence":"additional","affiliation":[{"name":"Dr. Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,16]]},"reference":[{"key":"ref_1","unstructured":"Musa, R., and Qurie, A. (2023, September 25). Raynaud Disease (Raynaud Phenomenon, Raynaud Syndrome). 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