---
_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. <i>Nature Communications</i>. 2018;9(1).
    doi:<a href="https://doi.org/10.1038/s41467-018-04342-1">10.1038/s41467-018-04342-1</a>
  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. <i>Nature Communications</i>. Springer Nature.
    <a href="https://doi.org/10.1038/s41467-018-04342-1">https://doi.org/10.1038/s41467-018-04342-1</a>
  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.” <i>Nature Communications</i>. Springer Nature, 2018. <a href="https://doi.org/10.1038/s41467-018-04342-1">https://doi.org/10.1038/s41467-018-04342-1</a>.
  ieee: M. Morri <i>et al.</i>, “Optical functionalization of human class A orphan
    G-protein-coupled receptors,” <i>Nature Communications</i>, 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.” <i>Nature Communications</i>, vol. 9, no. 1, 1950,
    Springer Nature, 2018, doi:<a href="https://doi.org/10.1038/s41467-018-04342-1">10.1038/s41467-018-04342-1</a>.
  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'
...