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dc.contributor.authorPadilla, BE
dc.contributor.authorCottrell, GS
dc.contributor.authorRoosterman, D
dc.contributor.authorPikios, S
dc.contributor.authorMuller, L
dc.contributor.authorSteinhoff, M
dc.contributor.authorBunnett, NW
dc.date.accessioned2021-02-04T01:45:27Z
dc.date.available2021-02-04T01:45:27Z
dc.date.issued2007-12-03
dc.identifierpii: jcb.200704053
dc.identifier.citationPadilla, B. E., Cottrell, G. S., Roosterman, D., Pikios, S., Muller, L., Steinhoff, M. & Bunnett, N. W. (2007). Endothelin-converting enzyme-1 regulates endosomal sorting of calcitonin receptor-like receptor and beta-arrestins. JOURNAL OF CELL BIOLOGY, 179 (5), pp.981-997. https://doi.org/10.1083/jcb.200704053.
dc.identifier.issn0021-9525
dc.identifier.urihttp://hdl.handle.net/11343/259466
dc.description.abstractAlthough 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-d) 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), beta-arrestin2, and ECE-1 to early endosomes, where ECE-1 degrades CGRP. CGRP degradation promotes CLR/RAMP1 recycling and beta-arrestin2 redistribution to the cytosol. ECE-1 inhibition or knockdown traps CLR/RAMP1 and beta-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 B(2) receptor, which transiently interacts with beta-arrestins. We propose a mechanism by which endosomal ECE-1 degrades neuropeptides in endosomes to disrupt the peptide/receptor/beta-arrestin complex, freeing internalized receptors from beta-arrestins and promoting recycling and resensitization.
dc.languageEnglish
dc.publisherROCKEFELLER UNIV PRESS
dc.titleEndothelin-converting enzyme-1 regulates endosomal sorting of calcitonin receptor-like receptor and beta-arrestins
dc.typeJournal Article
dc.identifier.doi10.1083/jcb.200704053
melbourne.affiliation.departmentPharmacology and Therapeutics
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleThe Journal of Cell Biology
melbourne.source.volume179
melbourne.source.issue5
melbourne.source.pages981-997
dc.rights.licenseCC BY-NC-SA
melbourne.elementsid1210735
melbourne.contributor.authorBunnett, Nigel
dc.identifier.eissn1540-8140
melbourne.accessrightsOpen Access


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