Antimuscarinic drugs exert β-arrestin–biased agonism at the muscarinic acetylcholine type 1 receptor to promote DRG neuritogenesis
or GPCR kinases (GRKs). Pharmacological or siRNA-based inhibition of CK2 blocked PZ-dependent β-arrestin recruitment, ERK activation, and neurite outgrowth in DRG neurons. These results implicate a GRK- and G protein-independent mechanism for the β-arrestin-biased agonism and antimuscarinic effects of PZ and MT7.
Authors
- Henry A. Dunn (ORCID: https://orcid.org/0000-0002-2543-4740)
- Mohamad‐Reza Aghanoori (ORCID: https://orcid.org/0000-0003-1495-748X)
- Ying Lao (ORCID: https://orcid.org/0000-0003-0868-1034)
- Paul Fernyhough (ORCID: https://orcid.org/0000-0002-9507-1201)
- Darrell R. Smith
- Rene P Zahedi
- Shayan Amiri
- Asuka Inoue
- T. M. Zaved Waise
Institutions
- Manitoba Health (CA)
- Tohoku University (JP)
- Kyoto University (JP)
- Kyoto Pharmaceutical University (JP)
- St. Boniface Hospital (CA)
- NeuroDevelopment Center (US)
- University of Manitoba (CA)
Publication Details
- Journal
- Science Signaling
- Published
- 2026-03-31
- DOI
- https://doi.org/10.1126/scisignal.ady7187
- Citations
- 1
- Primary Topic
- Receptor Mechanisms and Signaling
- Type
- article
- Field-Weighted Citation Impact
- 12.26
Funders
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- Japan Science and Technology Agency