Very large G protein-coupled receptor 1 regulates myelin-associated glycoprotein via G<sub>αs</sub>/G<sub>αq</sub>-mediated protein kinases A/C

Shin, Daesung; Lin, Shuting; Fu, Ying‐Hui; Ptáček, Louis J.

doi:10.1073/pnas.1318501110

Cited by 50 publications

(53 citation statements)

References 41 publications

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“…Similarly, several isoforms of ADGRV1 (VLGR1) were reported to be widely expressed in a spatiotemporally regulated manner (reviewed in McMillan and White, 2010). This receptor shows a particularly strong expression in sensory cells of the eye and the inner ear, as well as in the brain (van Wijk et al, 2006;Maerker et al, 2008;Zallocchi et al, 2012;Shin et al, 2013).…”

Section: Expressionmentioning

confidence: 99%

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International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors

et al. 2015

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Section: Expressionmentioning

confidence: 99%

“…More recently the expression of Adgrv1 (Vlgr1) in oligodendrocytes has also been described, and myelin-associated glycoprotein levels were reduced in the Frings mutant, suggesting a potential role in regulating myelination for this Adhesion GPCR (Shin et al, 2013).…”

Section: Skeletal Muscle and Bonementioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors

et al. 2015

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“…At later stages of development, the adhesion GPCR Gpr98/Adgrv1 (also previously called Very large GPCR-1 [Vlgr1]) is enriched in myelinating oligodendrocytes [72]. In cultured oligodendrocytes, loss of Gpr98/Adgrv1 decreases while overexpression of Gpr98/Adgrv1 increases levels of Myelin-associated glycoprotein (MAG), and MAG levels are also decreased in the CNS of Gpr98/Adgrv1 mutant mice [72].…”

Section: Adhesion Gpcrs In Oligodendrocyte Developmentmentioning

confidence: 99%

“…In cultured oligodendrocytes, loss of Gpr98/Adgrv1 decreases while overexpression of Gpr98/Adgrv1 increases levels of Myelin-associated glycoprotein (MAG), and MAG levels are also decreased in the CNS of Gpr98/Adgrv1 mutant mice [72]. These functions are thought to be mediated by Gpr98/Adgrv1's Gα s and Gα q G protein coupling abilities in response to extracellular calcium [72]. In all, recent work has firmly established several GPCRs as key regulators of oligodendryocyte development and CNS myelination.…”

Section: Adhesion Gpcrs In Oligodendrocyte Developmentmentioning

confidence: 99%

G Protein-Coupled Receptors in Myelinating Glia

Mogha¹,

D’Rozario²,

Monk

2017

Trends in Pharmacological Sciences

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The G protein-coupled receptor (GPCR) super-family represents the largest class of functionally selective drug targets for disease modulation and therapy. GPCRs have been studied in great detail in central nervous system (CNS) neurons, yet these important molecules have been relatively understudied in glia. In recent years, however, exciting new roles for GPCRs in glial cell biology have emerged. Here, we focus on key roles for GPCRs in a specialized subset of glia, myelinating glia. We highlight recent work firmly establishing GPCRs as regulators of myelinating glial cell development and myelin repair. These advancements expand our understanding of myelinating glial cell biology and underscore the utility of targeting GPCRs to promote myelin repair in human disease. KeywordsG protein-coupled receptor (GPCR); myelination; Schwann cell; oligodendrocyte; remyelination An overview of G protein-coupled receptors in the nervous systemThe G protein-coupled receptor (GPCR) super-family of seven transmembrane (7TM) receptors comprises the largest class of cell membrane receptors [1]. GPCRs are activated by myriad stimuli including peptides, hormones, light, proteolytic processing of their Ntermini, small molecules, and more traditional protein ligands [2,3]. GPCRs have emerged as major pharmacological drug targets due to their key roles in a variety of physiological functions in disease and health, and GPCR modulators represent at least one-third of all clinically marketed drugs [4]. GPCRs can be classified into five families using the phylogenetically based GRAFS system: glutamate, rhodopsin, adhesion, frizzled, and secretin [5]. Glutamate is a major excitatory neurotransmitter in the nervous system, and * Correspondence: monkk@wustl.edu (K.R. Monk). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conflict of interest statementThe authors declare no competing conflicts. HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript accordingly, glutamate receptors have been studied in great detail with regard to their key roles in synaptic transmission, synapse formation, axon guidance, and development of neuronal circuits [6,7]. The rhodopsin family has by far the greatest number of GPCRs, and members are involved in photoreception and neurotransmission [5]. Frizzled GPCRs are activated by wingless/int (Wnt) proteins and control numerous cellular processes including neural crest development, patterning and adult neurogenesis [8]. Secretin receptors are classic hormone receptors, some of which have neuroprotective functions in the central nervou...

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“…For example, GPR126 and GPR133 have been shown to interact with both G s and G i proteins Mogha et al, 2013). Similarly, GPR64 interacts with G s and G q proteins (Kirchhoff et al, 2006), GPR56 can couple to G q/11 (Little et al, 2004) as well as G 12/13 (Iguchi et al, 2008), and VLGR1 can couple to G i (Hu et al, 2014), G q , and G s proteins (Shin et al, 2013). While these studies measured basal G protein signaling, it will be interesting to examine G protein coupling specificities upon agonist activation.…”

Section: Adhesion Gpcr Pharmacologymentioning

confidence: 99%

Adhesion G Protein–Coupled Receptors: From In Vitro Pharmacology to In Vivo Mechanisms

et al. 2015

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The adhesion family of G protein-coupled receptors (aGPCRs) comprises 33 members in humans. aGPCRs are characterized by their enormous size and complex modular structures. While the physiologic importance of many aGPCRs has been clearly demonstrated in recent years, the underlying molecular functions have only recently begun to be elucidated. In this minireview, we present an overview of our current knowledge on aGPCR activation and signal transduction with a focus on the latest findings regarding the interplay between ligand binding, mechanical force, and the tethered agonistic Stachel sequence, as well as implications on translational approaches that may derive from understanding aGPCR pharmacology.

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Very large G protein-coupled receptor 1 regulates myelin-associated glycoprotein via G_αs/G_αq-mediated protein kinases A/C

Abstract: This article contains supporting information online at www.pnas.org/lookup/suppl

Cited by 50 publications

References 41 publications

International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors

International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors

G Protein-Coupled Receptors in Myelinating Glia

Adhesion G Protein–Coupled Receptors: From In Vitro Pharmacology to In Vivo Mechanisms

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Very large G protein-coupled receptor 1 regulates myelin-associated glycoprotein via Gαs/Gαq-mediated protein kinases A/C

Abstract: This article contains supporting information online at www.pnas.org/lookup/suppl

Cited by 50 publications

References 41 publications

International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors

International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors

G Protein-Coupled Receptors in Myelinating Glia

Adhesion G Protein–Coupled Receptors: From In Vitro Pharmacology to In Vivo Mechanisms

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Very large G protein-coupled receptor 1 regulates myelin-associated glycoprotein via G_αs/G_αq-mediated protein kinases A/C