--- _id: '6124' abstract: - lang: eng text: Despite the importance of G-protein coupled receptors (GPCRs) their biogenesis is poorly understood. Like vertebrates, C. elegans uses a large family of GPCRs as chemoreceptors. A subset of these receptors, such as ODR-10, requires the odr-4 and odr-8 genes to be appropriately localized to sensory cilia. The odr-4 gene encodes a conserved tail-anchored transmembrane protein; the molecular identity of odr-8 is unknown. Here, we show that odr-8 encodes the C. elegans ortholog of Ufm1-specific protease 2 (UfSP2). UfSPs are cysteine proteases identified biochemically by their ability to liberate the ubiquitin-like modifier Ufm1 from its pro-form and protein conjugates. ODR-8/UfSP2 and ODR-4 are expressed in the same set of twelve chemosensory neurons, and physically interact at the ER membrane. ODR-4 also binds ODR-10, suggesting that an ODR-4/ODR-8 complex promotes GPCR folding, maturation, or export from the ER. The physical interaction between human ODR4 and UfSP2 suggests that this complex's role in GPCR biogenesis may be evolutionarily conserved. Unexpectedly, mutant versions of ODR-8/UfSP2 lacking catalytic residues required for protease activity can rescue all odr-8 mutant phenotypes tested. Moreover, deleting C. elegans ufm-1 does not alter chemoreceptor traffic to cilia, either in wild type or in odr-8 mutants. Thus, UfSP2 proteins have protease- and Ufm1-independent functions in GPCR biogenesis. article_number: e1004082 author: - first_name: Changchun full_name: Chen, Changchun last_name: Chen - first_name: Eisuke full_name: Itakura, Eisuke last_name: Itakura - first_name: Katherine P. full_name: Weber, Katherine P. last_name: Weber - first_name: Ramanujan S. full_name: Hegde, Ramanujan S. last_name: Hegde - first_name: Mario full_name: de Bono, Mario id: 4E3FF80E-F248-11E8-B48F-1D18A9856A87 last_name: de Bono orcid: 0000-0001-8347-0443 citation: ama: Chen C, Itakura E, Weber KP, Hegde RS, de Bono M. An ER complex of ODR-4 and ODR-8/Ufm1 specific protease 2 promotes GPCR maturation by a Ufm1-independent mechanism. PLoS Genetics. 2014;10(3). doi:10.1371/journal.pgen.1004082 apa: Chen, C., Itakura, E., Weber, K. P., Hegde, R. S., & de Bono, M. (2014). An ER complex of ODR-4 and ODR-8/Ufm1 specific protease 2 promotes GPCR maturation by a Ufm1-independent mechanism. PLoS Genetics. Public Library of Science (PLoS). https://doi.org/10.1371/journal.pgen.1004082 chicago: Chen, Changchun, Eisuke Itakura, Katherine P. Weber, Ramanujan S. Hegde, and Mario de Bono. “An ER Complex of ODR-4 and ODR-8/Ufm1 Specific Protease 2 Promotes GPCR Maturation by a Ufm1-Independent Mechanism.” PLoS Genetics. Public Library of Science (PLoS), 2014. https://doi.org/10.1371/journal.pgen.1004082. ieee: C. Chen, E. Itakura, K. P. Weber, R. S. Hegde, and M. de Bono, “An ER complex of ODR-4 and ODR-8/Ufm1 specific protease 2 promotes GPCR maturation by a Ufm1-independent mechanism,” PLoS Genetics, vol. 10, no. 3. Public Library of Science (PLoS), 2014. ista: Chen C, Itakura E, Weber KP, Hegde RS, de Bono M. 2014. An ER complex of ODR-4 and ODR-8/Ufm1 specific protease 2 promotes GPCR maturation by a Ufm1-independent mechanism. PLoS Genetics. 10(3), e1004082. mla: Chen, Changchun, et al. “An ER Complex of ODR-4 and ODR-8/Ufm1 Specific Protease 2 Promotes GPCR Maturation by a Ufm1-Independent Mechanism.” PLoS Genetics, vol. 10, no. 3, e1004082, Public Library of Science (PLoS), 2014, doi:10.1371/journal.pgen.1004082. short: C. Chen, E. Itakura, K.P. Weber, R.S. Hegde, M. de Bono, PLoS Genetics 10 (2014). date_created: 2019-03-19T14:45:56Z date_published: 2014-03-06T00:00:00Z date_updated: 2021-01-12T08:06:14Z day: '06' ddc: - '570' doi: 10.1371/journal.pgen.1004082 extern: '1' external_id: pmid: - '24603482' file: - access_level: open_access checksum: ac19941089a4262bb5bd74434a08b003 content_type: application/pdf creator: kschuh date_created: 2019-03-19T14:50:07Z date_updated: 2020-07-14T12:47:20Z file_id: '6125' file_name: 2014_PLOS_Chen.PDF file_size: 8286819 relation: main_file file_date_updated: 2020-07-14T12:47:20Z has_accepted_license: '1' intvolume: ' 10' issue: '3' language: - iso: eng month: '03' oa: 1 oa_version: Published Version pmid: 1 publication: PLoS Genetics publication_identifier: issn: - 1553-7404 publication_status: published publisher: Public Library of Science (PLoS) quality_controlled: '1' status: public title: An ER complex of ODR-4 and ODR-8/Ufm1 specific protease 2 promotes GPCR maturation by a Ufm1-independent mechanism tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 10 year: '2014' ...