--- _id: '5984' abstract: - lang: eng text: G-protein-coupled receptors (GPCRs) form the largest receptor family, relay environmental stimuli to changes in cell behavior and represent prime drug targets. Many GPCRs are classified as orphan receptors because of the limited knowledge on their ligands and coupling to cellular signaling machineries. Here, we engineer a library of 63 chimeric receptors that contain the signaling domains of human orphan and understudied GPCRs functionally linked to the light-sensing domain of rhodopsin. Upon stimulation with visible light, we identify activation of canonical cell signaling pathways, including cAMP-, Ca2+-, MAPK/ERK-, and Rho-dependent pathways, downstream of the engineered receptors. For the human pseudogene GPR33, we resurrect a signaling function that supports its hypothesized role as a pathogen entry site. These results demonstrate that substituting unknown chemical activators with a light switch can reveal information about protein function and provide an optically controlled protein library for exploring the physiology and therapeutic potential of understudied GPCRs. article_number: '1950' article_processing_charge: No author: - first_name: Maurizio full_name: Morri, Maurizio id: 4863116E-F248-11E8-B48F-1D18A9856A87 last_name: Morri - first_name: Inmaculada full_name: Sanchez-Romero, Inmaculada id: 3D9C5D30-F248-11E8-B48F-1D18A9856A87 last_name: Sanchez-Romero - first_name: Alexandra-Madelaine full_name: Tichy, Alexandra-Madelaine id: 29D8BB2C-F248-11E8-B48F-1D18A9856A87 last_name: Tichy - first_name: Stephanie full_name: Kainrath, Stephanie id: 32CFBA64-F248-11E8-B48F-1D18A9856A87 last_name: Kainrath - first_name: Elliot J. full_name: Gerrard, Elliot J. last_name: Gerrard - first_name: Priscila full_name: Hirschfeld, Priscila id: 435ACB3A-F248-11E8-B48F-1D18A9856A87 last_name: Hirschfeld - first_name: Jan full_name: Schwarz, Jan id: 346C1EC6-F248-11E8-B48F-1D18A9856A87 last_name: Schwarz - first_name: Harald L full_name: Janovjak, Harald L id: 33BA6C30-F248-11E8-B48F-1D18A9856A87 last_name: Janovjak orcid: 0000-0002-8023-9315 citation: ama: Morri M, Sanchez-Romero I, Tichy A-M, et al. Optical functionalization of human class A orphan G-protein-coupled receptors. Nature Communications. 2018;9(1). doi:10.1038/s41467-018-04342-1 apa: Morri, M., Sanchez-Romero, I., Tichy, A.-M., Kainrath, S., Gerrard, E. J., Hirschfeld, P., … Janovjak, H. L. (2018). Optical functionalization of human class A orphan G-protein-coupled receptors. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-018-04342-1 chicago: Morri, Maurizio, Inmaculada Sanchez-Romero, Alexandra-Madelaine Tichy, Stephanie Kainrath, Elliot J. Gerrard, Priscila Hirschfeld, Jan Schwarz, and Harald L Janovjak. “Optical Functionalization of Human Class A Orphan G-Protein-Coupled Receptors.” Nature Communications. Springer Nature, 2018. https://doi.org/10.1038/s41467-018-04342-1. ieee: M. Morri et al., “Optical functionalization of human class A orphan G-protein-coupled receptors,” Nature Communications, vol. 9, no. 1. Springer Nature, 2018. ista: Morri M, Sanchez-Romero I, Tichy A-M, Kainrath S, Gerrard EJ, Hirschfeld P, Schwarz J, Janovjak HL. 2018. Optical functionalization of human class A orphan G-protein-coupled receptors. Nature Communications. 9(1), 1950. mla: Morri, Maurizio, et al. “Optical Functionalization of Human Class A Orphan G-Protein-Coupled Receptors.” Nature Communications, vol. 9, no. 1, 1950, Springer Nature, 2018, doi:10.1038/s41467-018-04342-1. short: M. Morri, I. Sanchez-Romero, A.-M. Tichy, S. Kainrath, E.J. Gerrard, P. Hirschfeld, J. Schwarz, H.L. Janovjak, Nature Communications 9 (2018). date_created: 2019-02-14T10:50:24Z date_published: 2018-12-01T00:00:00Z date_updated: 2023-09-19T14:29:32Z day: '01' ddc: - '570' department: - _id: HaJa - _id: CaGu - _id: MiSi doi: 10.1038/s41467-018-04342-1 ec_funded: 1 external_id: isi: - '000432280000006' file: - access_level: open_access checksum: 8325fcc194264af4749e662a73bf66b5 content_type: application/pdf creator: kschuh date_created: 2019-02-14T10:58:29Z date_updated: 2020-07-14T12:47:14Z file_id: '5985' file_name: 2018_Springer_Morri.pdf file_size: 1349914 relation: main_file file_date_updated: 2020-07-14T12:47:14Z has_accepted_license: '1' intvolume: ' 9' isi: 1 issue: '1' language: - iso: eng month: '12' oa: 1 oa_version: Published Version project: - _id: 25548C20-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '303564' name: Microbial Ion Channels for Synthetic Neurobiology - _id: 255A6082-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets publication: Nature Communications publication_identifier: issn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Optical functionalization of human class A orphan G-protein-coupled receptors 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 9 year: '2018' ...