{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T03:26:50Z","timestamp":1767929210482,"version":"3.49.0"},"reference-count":51,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,12,3]]},"abstract":"<jats:p>Although cell surface metalloendopeptidases degrade neuropeptides in the extracellular fluid to terminate signaling, the function of peptidases in endosomes is unclear. We report that isoforms of endothelin-converting enzyme-1 (ECE-1a\u2013d) are present in early endosomes, where they degrade neuropeptides and regulate post-endocytic sorting of receptors. Calcitonin gene-related peptide (CGRP) co-internalizes with calcitonin receptor-like receptor (CLR), receptor activity-modifying protein 1 (RAMP1), \u03b2-arrestin2, and ECE-1 to early endosomes, where ECE-1 degrades CGRP. CGRP degradation promotes CLR\/RAMP1 recycling and \u03b2-arrestin2 redistribution to the cytosol. ECE-1 inhibition or knockdown traps CLR\/RAMP1 and \u03b2-arrestin2 in endosomes and inhibits CLR\/RAMP1 recycling and resensitization, whereas ECE-1 overexpression has the opposite effect. ECE-1 does not regulate either the resensitization of receptors for peptides that are not ECE-1 substrates (e.g., angiotensin II), or the recycling of the bradykinin B2 receptor, which transiently interacts with \u03b2-arrestins. We propose a mechanism by which endosomal ECE-1 degrades neuropeptides in endosomes to disrupt the peptide\/receptor\/\u03b2-arrestin complex, freeing internalized receptors from \u03b2-arrestins and promoting recycling and resensitization.<\/jats:p>","DOI":"10.1083\/jcb.200704053","type":"journal-article","created":{"date-parts":[[2007,11,27]],"date-time":"2007-11-27T04:58:26Z","timestamp":1196139506000},"page":"981-997","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":92,"title":["Endothelin-converting enzyme-1 regulates endosomal sorting of calcitonin receptor-like receptor and \u03b2-arrestins"],"prefix":"10.1083","volume":"179","author":[{"given":"Benjamin E.","family":"Padilla","sequence":"first","affiliation":[{"name":"1Departments of Surgery and Physiology, University of California, San Francisco, San Francisco, CA 94143"}]},{"given":"Graeme S.","family":"Cottrell","sequence":"additional","affiliation":[{"name":"1Departments of Surgery and Physiology, University of California, San Francisco, San Francisco, CA 94143"}]},{"given":"Dirk","family":"Roosterman","sequence":"additional","affiliation":[{"name":"2Department of Dermatology, Interdisciplinary Center for Clinical Research, and the Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, University of Mu\u0308nster, 48149 Mu\u0308nster, Germany"}]},{"given":"Stella","family":"Pikios","sequence":"additional","affiliation":[{"name":"1Departments of Surgery and Physiology, University of California, San Francisco, San Francisco, CA 94143"}]},{"given":"Laurent","family":"Muller","sequence":"additional","affiliation":[{"name":"3INSERM U 36 College de France Paris, 75005 Paris, France"}]},{"given":"Martin","family":"Steinhoff","sequence":"additional","affiliation":[{"name":"2Department of Dermatology, Interdisciplinary Center for Clinical Research, and the Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, University of Mu\u0308nster, 48149 Mu\u0308nster, Germany"}]},{"given":"Nigel W.","family":"Bunnett","sequence":"additional","affiliation":[{"name":"1Departments of Surgery and Physiology, University of California, San Francisco, San Francisco, CA 94143"}]}],"member":"291","published-online":{"date-parts":[[2007,11,26]]},"reference":[{"key":"2023072909220564100_BIB1","doi-asserted-by":"crossref","first-page":"33723","DOI":"10.1074\/jbc.274.47.33723","volume":"274","year":"1999","journal-title":"J. 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