title: Role of Regulators of G Protein Signaling Proteins in Bone Physiology and Pathophysiology.
abstract: Regulators of G protein signaling (RGS) proteins enhance the intrinsic GTPase activity of α subunits of the heterotrimeric G protein complex of G protein-coupled receptors (GPCRs) and thereby inactivate signal transduction initiated by GPCRs. The RGS family consists of nearly 37 members with a conserved RGS homology domain which is critical for their GTPase accelerating activity. RGS proteins are expressed in most tissues, including heart, lung, brain, kidney, and bone and play essential roles in many physiological and pathological processes. In skeletal development and bone homeostasis as well as in many bone disorders, RGS proteins control the functions of various GPCRs, including the parathyroid hormone receptor type 1 and calcium-sensing receptor and also regulate various critical signaling pathways, such as Wnt and calcium oscillations. This chapter will discuss the current findings on the roles of RGS proteins in regulating signaling of key GPCRs in skeletal development and bone homeostasis. We also will examine the current updates of RGS proteins' regulation of calcium oscillations in bone physiology and highlight the roles of RGS proteins in selected bone pathological disorders. Despite the recent advances in bone and mineral research, RGS proteins remain understudied in the skeletal system. Further understanding of the roles of RGS proteins in bone should not only provide great insights into the molecular basis of various bone diseases but also generate great therapeutic drug targets for many bone diseases.
authors.affiliation: Department of Pathology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Jules
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, New York, USA; Developmental Genomics Group, New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, The State University of New York, Buffalo, New York, USA.
authors.forename: Shuying
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Pathology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Pathology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. Electronic address: ypli@uab.edu.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Li
mesh_terms: D000818:Animals; D001847:Bone Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D008954:Models, Biological; D020710:RGS Proteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020710:RGS Proteins; D043562:Receptors, G-Protein-Coupled
keywords: Bone; Bone homeostasis; G protein-coupled receptors; G proteins; Osteoblasts; Osteoclasts; PTH/PTHrP; Regulators of G protein signaling; Skeletal disorders; Wnt