Constitutive Gαi Coupling Activity of Very Large G Protein-coupled Receptor 1 (VLGR1) and Its Regulation by PDZD7 Protein

Hu, Qiao Xia; Dong, Jun; Du, Hai Bo; Zhang, Dao Lai; Ren, Hong; Liang, Ming; Cai, Yuan; Zhao, Tong; Yin, Xiao Lei; Yu, Xiao; Xue, Tian; Xu, Zhi; Sun, Jin Peng

doi:10.1074/jbc.m114.549816

Cited by 68 publications

(80 citation statements)

References 36 publications

(50 reference statements)

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“…VLGR1 protein was shown to sense the extracellular calcium changes and activate PKA and PKC through binding to Gαs and Gαq, respectively, in the superior and inferior colliculi [70]. This protein was also demonstrated to couple Gαi signaling in over-expressed cell cultures [173]. These signaling pathways could therefore co-exist at the VLGR1-containing USH2 protein complex in both hair cells and photoreceptors.…”

Section: Insights From Current Literatures About Ush Genes In Varimentioning

confidence: 99%

Usher syndrome: Hearing loss, retinal degeneration and associated abnormalities

Mathur

Yang

2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

279

301

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Usher syndrome (USH), clinically and genetically heterogeneous, is the leading genetic cause of combined hearing and vision loss. USH is classified into three types, based on the hearing and vestibular symptoms observed in patients. Sixteen loci have been reported to be involved in the occurrence of USH and atypical USH. Among them, twelve have been identified as causative genes and one as a modifier gene. Studies on the proteins encoded by these USH genes suggest that USH proteins interact among one another and function in multiprotein complexes in vivo. Although their exact functions remain enigmatic in the retina, USH proteins are required for the development, maintenance and function of hair bundles, which are the primary mechanosensitive structure of inner ear hair cells. Despite the unavailability of a cure, progress has been made to develop effective treatments for this disease. In this review, we focus on the most recent discoveries in the field with an emphasis on USH genes, protein complexes and functions in various tissues as well as progress toward therapeutic development for USH.

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Section: Insights From Current Literatures About Ush Genes In Varimentioning

confidence: 99%

Usher syndrome: Hearing loss, retinal degeneration and associated abnormalities

Mathur

Yang

2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

279

301

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“…Recently, collagen IV was shown to stimulate cAMP signaling in cells expressing ADGRG6 (Gpr126) (Paavola et al, 2014). Additionally, in vitro analysis showed Ga s and Ga i coupling for ADGRG6 (GPR126) and Ga i coupling for ADGRV1 (VLGR1) (Hu et al, 2014).…”

Section: A G Protein-mediated Intracellular Signalingmentioning

confidence: 99%

“…The second scenario might be more likely, since all other known GPCRs signal via an agonist-driven switch-on mechanism. Similar mechanisms may facilitate inhibitory functions of Adhesion GPCRs, e.g., the CTF of ADGRV1 (VLGR1) alone inhibits adenylate cyclase activity through Ga i coupling (Hu et al, 2014).…”

Section: Modes Of Signalingmentioning

confidence: 99%

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

et al. 2015

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“…We therefore applied the Gi inhibitor pertussis toxin in U251 cells (31,32). Preincubation of U251 cells with pertussis toxin caused no significant change in lactate release or expression levels of LDHA, MCT1, and MCT4 (Figure 4D–F).…”

Section: Resultsmentioning

confidence: 99%

Adaptive Activation of a Stress Response Pathway Improves Learning and Memory Through Gs and β-Arrestin-1–Regulated Lactate Metabolism

Dong

Wang

Cui

et al. 2017

Biological Psychiatry

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BACKGROUND: Stress is a conserved physiological response in mammals. Whereas moderate stress strengthens memory to improve reactions to previously experienced difficult situations, too much stress is harmful. METHODS: We used specific β-adrenergic agonists, as well as β2-adrenergic receptor (β2AR) and arrestin knockout models, to study the effects of adaptive β2AR activation on cognitive function using Morris water maze and object recognition experiments. We used molecular and cell biological approaches to elucidate the signaling subnetworks. RESULTS: We observed that the duration of the adaptive β2AR activation determines its consequences on learning and memory. Short-term formoterol treatment, for 3 to 5 days, improved cognitive function; however, prolonged β2AR activation, for more than 6 days, produced harmful effects. We identified the activation of several signaling networks downstream of β2AR, as well as an essential role for arrestin and lactate metabolism in promoting cognitive ability. Whereas Gs–protein kinase A–cyclic adenosine monophosphate response element binding protein signaling modulated monocarboxylate transporter 1 expression, β-arrestin-1 controlled expression levels of monocarboxylate transporter 4 and lactate dehydrogenase A through the formation of a β-arrestin-1/phospho-mitogen-activated protein kinase/hypoxia-inducible factor-1α ternary complex to upregulate lactate metabolism in astrocyte-derived U251 cells. Conversely, long-term treatment with formoterol led to the desensitization of β2ARs, which was responsible for its decreased beneficial effects. CONCLUSIONS: Our results not only revealed that β-arrestin-1 regulated lactate metabolism to contribute to β2AR functions in improved memory formation, but also indicated that the appropriate management of one specific stress pathway, such as through the clinical drug formoterol, may exert beneficial effects on cognitive abilities.

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Constitutive Gαi Coupling Activity of Very Large G Protein-coupled Receptor 1 (VLGR1) and Its Regulation by PDZD7 Protein

Cited by 68 publications

References 36 publications

Usher syndrome: Hearing loss, retinal degeneration and associated abnormalities

Usher syndrome: Hearing loss, retinal degeneration and associated abnormalities

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

Adaptive Activation of a Stress Response Pathway Improves Learning and Memory Through Gs and β-Arrestin-1–Regulated Lactate Metabolism

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