title: GRK2: putting the brakes on the circadian clock.
abstract: G protein-coupled receptor kinases (GRKs) are a family of serine/threonine protein kinases that terminate G protein-coupled receptor (GPCR) signaling by phosphorylating the receptor and inducing its internalization. In addition to their canonical function, some GRKs can phosphorylate non-GPCR substrates and regulate GPCR signaling in a kinase-independent manner. GPCRs are abundantly expressed in the suprachiasmatic nucleus (SCN), a structure in the mammalian brain that serves as the central circadian pacemaker. Various facets of circadian timekeeping are under the influence of GPCR signaling, and thus are potential targets for GRK regulation. Despite this, little attention has been given to the role of GRKs in circadian rhythms. In this research highlight, we discuss our latest findings on the functional involvement of GRK2 in mammalian circadian timekeeping in the SCN. Usinggrk2knockout mice, we demonstrate that GRK2 is critical for maintaining proper clock speed and ensuring that the clock is appropriately synchronized to environmental light cycles. Althoughgrk2deficiency expectedly alters the expression of a key GPCR in the SCN, our study also reveals that GRK2 has a more direct function that touches the heart of the circadian clock.
authors.affiliation: Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada; Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON M5S 3G5, Canada.
authors.forename: Lucia
authors.initials: L
authors.lastname: Mendoza-Viveros
authors.affiliation: Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada; Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON M5S 3G5, Canada.
authors.forename: Arthur H
authors.initials: AH
authors.lastname: Cheng
authors.affiliation: Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada; Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON M5S 3G5, Canada.
authors.forename: Hai-Ying M
authors.initials: HM
authors.lastname: Cheng
keywords: G protein-coupled receptor kinases; GPCR; GRK2; PERIOD proteins; circadian rhythms; light; nuclear trafficking; phosphorylation; suprachiasmatic nucleus; transcription