Proton-Gated Coincidence Detection Is a Common Feature of GPCR Signaling
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A 3' UTR SNP Rs885863, a Cis-Eqtl for the Circadian Gene VIPR2 and Lincrna 689, Is Associated with Opioid Addiction
RESEARCH ARTICLE A 3' UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction 1 1 2 3 4 Orna LevranID *, Matthew Randesi , John Rotrosen , Jurg Ott , Miriam Adelson , Mary Jeanne Kreek1 1 The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, New York, United States of America, 2 NYU School of Medicine, New York, New York, United States of America, 3 The Laboratory of Statistical Genetics, The Rockefeller University, New York, New York, United States of a1111111111 America, 4 Dr. Miriam and Sheldon G. Adelson Clinic for Drug Abuse Treatment and Research, Las Vegas, a1111111111 Nevada, United States of America a1111111111 a1111111111 * [email protected] a1111111111 Abstract There is a reciprocal relationship between the circadian and the reward systems. Polymor- OPEN ACCESS phisms in several circadian rhythm-related (clock) genes were associated with drug addic- Citation: Levran O, Randesi M, Rotrosen J, Ott J, tion. This study aims to search for associations between 895 variants in 39 circadian Adelson M, Kreek MJ (2019) A 3' UTR SNP rhythm-related genes and opioid addiction (OUD). Genotyping was performed with the rs885863, a cis-eQTL for the circadian gene VIPR2 ® and lincRNA 689, is associated with opioid Smokescreen array. Ancestry was verified by principal/MDS component analysis and the addiction. PLoS ONE 14(11): e0224399. https:// sample was limited to European Americans (EA) (OUD; n = 435, controls; n = 138). Nomi- doi.org/10.1371/journal.pone.0224399 nally significant associations (p < 0.01) were detected for several variants in genes encoding Editor: Huiping Zhang, Boston University, UNITED vasoactive intestinal peptide receptor 2 (VIPR2), period circadian regulator 2 (PER2), STATES casein kinase 1 epsilon (CSNK1E), and activator of transcription and developmental regula- Received: August 22, 2019 tor (AUTS2), but no signal survived correction for multiple testing. -
Lysophosphatidic Acid and Its Receptors: Pharmacology and Therapeutic Potential in Atherosclerosis and Vascular Disease
JPT-107404; No of Pages 13 Pharmacology & Therapeutics xxx (2019) xxx Contents lists available at ScienceDirect Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/pharmthera Lysophosphatidic acid and its receptors: pharmacology and therapeutic potential in atherosclerosis and vascular disease Ying Zhou a, Peter J. Little a,b, Hang T. Ta a,c, Suowen Xu d, Danielle Kamato a,b,⁎ a School of Pharmacy, University of Queensland, Pharmacy Australia Centre of Excellence, Woolloongabba, QLD 4102, Australia b Department of Pharmacy, Xinhua College of Sun Yat-sen University, Tianhe District, Guangzhou 510520, China c Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, St Lucia, QLD 4072, Australia d Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA article info abstract Available online xxxx Lysophosphatidic acid (LPA) is a collective name for a set of bioactive lipid species. Via six widely distributed G protein-coupled receptors (GPCRs), LPA elicits a plethora of biological responses, contributing to inflammation, Keywords: thrombosis and atherosclerosis. There have recently been considerable advances in GPCR signaling especially Lysophosphatidic acid recognition of the extended role for GPCR transactivation of tyrosine and serine/threonine kinase growth factor G-protein coupled receptors receptors. This review covers LPA signaling pathways in the light of new information. The use of transgenic and Atherosclerosis gene knockout animals, gene manipulated cells, pharmacological LPA receptor agonists and antagonists have Gproteins fi β-arrestins provided many insights into the biological signi cance of LPA and individual LPA receptors in the progression Transactivation of atherosclerosis and vascular diseases. -
Genetic Variations Influence Brain Changes in Patients with Attention
Yadav et al. Translational Psychiatry (2021) 11:349 https://doi.org/10.1038/s41398-021-01473-w Translational Psychiatry REVIEW ARTICLE Open Access Genetic variations influence brain changes in patients with attention-deficit hyperactivity disorder Santosh K. Yadav1,AjazA.Bhat 1, Sheema Hashem1,SabahNisar1, Madeeha Kamal2,NajeebSyed3, Mohamed-Ramzi Temanni3, Rakesh K. Gupta4, Saddat Kamran 5, Muhammad Waqar Azeem6, Amit K. Srivastava7, Puneet Bagga8, Sanjeev Chawla9, Ravinder Reddy10, Michael P. Frenneaux11, Khalid Fakhro 12,13 and Mohammad Haris 1,14 Abstract Attention-deficit hyperactivity disorder (ADHD) is a neurological and neurodevelopmental childhood-onset disorder characterized by a persistent pattern of inattentiveness, impulsiveness, restlessness, and hyperactivity. These symptoms may continue in 55–66% of cases from childhood into adulthood. Even though the precise etiology of ADHD is not fully understood, it is considered as a multifactorial and heterogeneous disorder with several contributing factors such as heritability, auxiliary to neurodevelopmental issues, severe brain injuries, neuroinflammation, consanguineous marriages, premature birth, and exposure to environmental toxins. Neuroimaging and neurodevelopmental assessments may help to explore the possible role of genetic variations on ADHD neuropsychobiology. Multiple genetic studies have observed a strong genetic association with various aspects of neuropsychobiological functions, including neural abnormalities and delayed neurodevelopment in ADHD. The advancement in neuroimaging and 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; molecular genomics offers the opportunity to analyze the impact of genetic variations alongside its dysregulated pathways on structural and functional derived brain imaging phenotypes in various neurological and psychiatric disorders, including ADHD. Recently, neuroimaging genomic studies observed a significant association of brain imaging phenotypes with genetic susceptibility in ADHD. -
Genome-Wide Prediction of Small Molecule Binding to Remote
bioRxiv preprint doi: https://doi.org/10.1101/2020.08.04.236729; this version posted August 5, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Genome-wide Prediction of Small Molecule Binding 2 to Remote Orphan Proteins Using Distilled Sequence 3 Alignment Embedding 1 2 3 4 4 Tian Cai , Hansaim Lim , Kyra Alyssa Abbu , Yue Qiu , 5,6 1,2,3,4,7,* 5 Ruth Nussinov , and Lei Xie 1 6 Ph.D. Program in Computer Science, The Graduate Center, The City University of New York, New York, 10016, USA 2 7 Ph.D. Program in Biochemistry, The Graduate Center, The City University of New York, New York, 10016, USA 3 8 Department of Computer Science, Hunter College, The City University of New York, New York, 10065, USA 4 9 Ph.D. Program in Biology, The Graduate Center, The City University of New York, New York, 10016, USA 5 10 Computational Structural Biology Section, Basic Science Program, Frederick National Laboratory for Cancer Research, 11 Frederick, MD 21702, USA 6 12 Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel 13 Aviv, Israel 7 14 Helen and Robert Appel Alzheimer’s Disease Research Institute, Feil Family Brain & Mind Research Institute, Weill 15 Cornell Medicine, Cornell University, New York, 10021, USA * 16 [email protected] 17 July 27, 2020 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.08.04.236729; this version posted August 5, 2020. -
The Role of the Mtor Pathway in Developmental Reprogramming Of
THE ROLE OF THE MTOR PATHWAY IN DEVELOPMENTAL REPROGRAMMING OF HEPATIC LIPID METABOLISM AND THE HEPATIC TRANSCRIPTOME AFTER EXPOSURE TO 2,2',4,4'- TETRABROMODIPHENYL ETHER (BDE-47) An Honors Thesis Presented By JOSEPH PAUL MCGAUNN Approved as to style and content by: ________________________________________________________** Alexander Suvorov 05/18/20 10:40 ** Chair ________________________________________________________** Laura V Danai 05/18/20 10:51 ** Committee Member ________________________________________________________** Scott C Garman 05/18/20 10:57 ** Honors Program Director ABSTRACT An emerging hypothesis links the epidemic of metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD) and diabetes with chemical exposures during development. Evidence from our lab and others suggests that developmental exposure to environmentally prevalent flame-retardant BDE47 may permanently reprogram hepatic lipid metabolism, resulting in an NAFLD-like phenotype. Additionally, we have demonstrated that BDE-47 alters the activity of both mTOR complexes (mTORC1 and 2) in hepatocytes. The mTOR pathway integrates environmental information from different signaling pathways, and regulates key cellular functions such as lipid metabolism, innate immunity, and ribosome biogenesis. Thus, we hypothesized that the developmental effects of BDE-47 on liver lipid metabolism are mTOR-dependent. To assess this, we generated mice with liver-specific deletions of mTORC1 or mTORC2 and exposed these mice and their respective controls perinatally to -
Edinburgh Research Explorer
Edinburgh Research Explorer International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list Citation for published version: Davenport, AP, Alexander, SPH, Sharman, JL, Pawson, AJ, Benson, HE, Monaghan, AE, Liew, WC, Mpamhanga, CP, Bonner, TI, Neubig, RR, Pin, JP, Spedding, M & Harmar, AJ 2013, 'International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands', Pharmacological reviews, vol. 65, no. 3, pp. 967-86. https://doi.org/10.1124/pr.112.007179 Digital Object Identifier (DOI): 10.1124/pr.112.007179 Link: Link to publication record in Edinburgh Research Explorer Document Version: Publisher's PDF, also known as Version of record Published In: Pharmacological reviews Publisher Rights Statement: U.S. Government work not protected by U.S. copyright General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 02. Oct. 2021 1521-0081/65/3/967–986$25.00 http://dx.doi.org/10.1124/pr.112.007179 PHARMACOLOGICAL REVIEWS Pharmacol Rev 65:967–986, July 2013 U.S. -
Melatonin-The Hormone of Darkness - O
PHYSIOLOGY AND MAINTENANCE – Vol. III - Melatonin-The Hormone of Darkness - O. Vakkuri MELATONIN―THE HORMONE OF DARKNESS O. Vakkuri Department of Physiology, University of Oulu, Finland. Keywords: Pineal gland, retina, suprachiasmatic nuclei, circadian and circannual rhythms. Contents 1. Introduction 2. Melatonin as Pineal Hormone of Darkness 3. Melatonin in Other Tissues 4. Circadian Secretion Pattern of Melatonin 5. Seasonal Secretion of Melatonin 6. Metabolism of Melatonin 7. Melatonin Receptors 8. Biological Action Profile of Melatonin 8.1. Melatonin and Sleep 8.2. Melatonin as Antioxidant and Cancer 8.3. Melatonin, Mental Health and Aging 9. Future Perspectives 10. Conclusions Glossary Bibliography Biographical Sketch Summary Melatonin, the pineal hormone of darkness, was originally found and chemically characterized to N-acetyl-5-methoxytryptamine in bovine pineal extracts in the late 1950s. Since then melatonin has been studied more and more intensively and not only in humans and several animal species but lately also in plants. After its first-described biological effect, i.e. skin-lightening effect in lower vertebrates, melatonin was shortly known as a rhythm marker due to its circadian biosynthesis and secretion pattern in the pineal gland: melatonin is synthesized and secreted during the night, i.e. the dark period of the day.UNESCO This circadian rhythm is endoge – nouslyEOLSS regulated by the biological clock in the suprachiasmatic nuclei of the hypothalamus. Environmental light has a clear inhibiting effectSAMPLE on melatonin biosynthesis, CHAPTERS continuously entraining the melatonin rhythm so that endogenous and exogenous rhythms are maintained in the same phase. The entraining light information is transmitting via the eyes and the retinohypothalamic tract to the suprachiasmatic nuclei and then via the paraventricular nuclei to superior cervical ganglia from which along the sympathetic tract finally to the pineal gland. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Supplementary Table 4
Li et al. mir-30d in human cancer Table S4. The probe list down-regulated in MDA-MB-231 cells by mir-30d mimic transfection Gene Probe Gene symbol Description Row set 27758 8119801 ABCC10 ATP-binding cassette, sub-family C (CFTR/MRP), member 10 15497 8101675 ABCG2 ATP-binding cassette, sub-family G (WHITE), member 2 18536 8158725 ABL1 c-abl oncogene 1, receptor tyrosine kinase 21232 8058591 ACADL acyl-Coenzyme A dehydrogenase, long chain 12466 7936028 ACTR1A ARP1 actin-related protein 1 homolog A, centractin alpha (yeast) 18102 8056005 ACVR1 activin A receptor, type I 20790 8115490 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 15688 7979904 ADAM21 ADAM metallopeptidase domain 21 14937 8054254 AFF3 AF4/FMR2 family, member 3 23560 8121277 AIM1 absent in melanoma 1 20209 7921434 AIM2 absent in melanoma 2 19272 8136336 AKR1B10 aldo-keto reductase family 1, member B10 (aldose reductase) 18013 7954777 ALG10 asparagine-linked glycosylation 10, alpha-1,2-glucosyltransferase homolog (S. pombe) 30049 7954789 ALG10B asparagine-linked glycosylation 10, alpha-1,2-glucosyltransferase homolog B (yeast) 28807 7962579 AMIGO2 adhesion molecule with Ig-like domain 2 5576 8112596 ANKRA2 ankyrin repeat, family A (RFXANK-like), 2 23414 7922121 ANKRD36BL1 ankyrin repeat domain 36B-like 1 (pseudogene) 29782 8098246 ANXA10 annexin A10 22609 8030470 AP2A1 adaptor-related protein complex 2, alpha 1 subunit 14426 8107421 AP3S1 adaptor-related protein complex 3, sigma 1 subunit 12042 8099760 ARAP2 ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 2 30227 8059854 ARL4C ADP-ribosylation factor-like 4C 32785 8143766 ARP11 actin-related Arp11 6497 8052125 ASB3 ankyrin repeat and SOCS box-containing 3 24269 8128592 ATG5 ATG5 autophagy related 5 homolog (S. -
Supplementary Material
Supplementary Material Table S1: Significant downregulated KEGGs pathways identified by DAVID following exposure to five cinnamon- based phenylpropanoids (p < 0.05). p-value Term: Genes (Benjamini) Cytokine-cytokine receptor interaction: FASLG, TNFSF14, CXCL11, IL11, FLT3LG, CCL3L1, CCL3L3, CXCR6, XCR1, 2.43 × 105 RTEL1, CSF2RA, TNFRSF17, TNFRSF14, CCNL2, VEGFB, AMH, TNFRSF10B, INHBE, IFNB1, CCR3, VEGFA, CCR2, IL12A, CCL1, CCL3, CXCL5, TNFRSF25, CCR1, CSF1, CX3CL1, CCL7, CCL24, TNFRSF1B, IL12RB1, CCL21, FIGF, EPO, IL4, IL18R1, FLT1, TGFBR1, EDA2R, HGF, TNFSF8, KDR, LEP, GH2, CCL13, EPOR, XCL1, IFNA16, XCL2 Neuroactive ligand-receptor interaction: OPRM1, THRA, GRIK1, DRD2, GRIK2, TACR2, TACR1, GABRB1, LPAR4, 9.68 × 105 GRIK5, FPR1, PRSS1, GNRHR, FPR2, EDNRA, AGTR2, LTB4R, PRSS2, CNR1, S1PR4, CALCRL, TAAR5, GABRE, PTGER1, GABRG3, C5AR1, PTGER3, PTGER4, GABRA6, GABRA5, GRM1, PLG, LEP, CRHR1, GH2, GRM3, SSTR2, Chlorogenic acid Chlorogenic CHRM3, GRIA1, MC2R, P2RX2, TBXA2R, GHSR, HTR2C, TSHR, LHB, GLP1R, OPRD1 Hematopoietic cell lineage: IL4, CR1, CD8B, CSF1, FCER2, GYPA, ITGA2, IL11, GP9, FLT3LG, CD38, CD19, DNTT, 9.29 × 104 GP1BB, CD22, EPOR, CSF2RA, CD14, THPO, EPO, HLA-DRA, ITGA2B Cytokine-cytokine receptor interaction: IL6ST, IL21R, IL19, TNFSF15, CXCR3, IL15, CXCL11, TGFB1, IL11, FLT3LG, CXCL10, CCR10, XCR1, RTEL1, CSF2RA, IL21, CCNL2, VEGFB, CCR8, AMH, TNFRSF10C, IFNB1, PDGFRA, EDA, CXCL5, TNFRSF25, CSF1, IFNW1, CNTFR, CX3CL1, CCL5, TNFRSF4, CCL4, CCL27, CCL24, CCL25, CCL23, IFNA6, IFNA5, FIGF, EPO, AMHR2, IL2RA, FLT4, TGFBR2, EDA2R, -
Individual Protomers of a G Protein-Coupled Receptor Dimer Integrate Distinct Functional Modules
OPEN Citation: Cell Discovery (2015) 1, 15011; doi:10.1038/celldisc.2015.11 © 2015 SIBS, CAS All rights reserved 2056-5968/15 ARTICLE www.nature.com/celldisc Individual protomers of a G protein-coupled receptor dimer integrate distinct functional modules Nathan D Camp1, Kyung-Soon Lee2, Jennifer L Wacker-Mhyre2, Timothy S Kountz2, Ji-Min Park2, Dorathy-Ann Harris2, Marianne Estrada2, Aaron Stewart2, Alejandro Wolf-Yadlin1, Chris Hague2 1Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA; 2Department of Pharmacology, University of Washington School of Medicine, Seattle, WA, USA Recent advances in proteomic technology reveal G-protein-coupled receptors (GPCRs) are organized as large, macromolecular protein complexes in cell membranes, adding a new layer of intricacy to GPCR signaling. We previously reported the α1D-adrenergic receptor (ADRA1D)—a key regulator of cardiovascular, urinary and CNS function—binds the syntrophin family of PDZ domain proteins (SNTA, SNTB1, and SNTB2) through a C-terminal PDZ ligand inter- action, ensuring receptor plasma membrane localization and G-protein coupling. To assess the uniqueness of this novel GPCR complex, 23 human GPCRs containing Type I PDZ ligands were subjected to TAP/MS proteomic analysis. Syntrophins did not interact with any other GPCRs. Unexpectedly, a second PDZ domain protein, scribble (SCRIB), was detected in ADRA1D complexes. Biochemical, proteomic, and dynamic mass redistribution analyses indicate syntrophins and SCRIB compete for the PDZ ligand, simultaneously exist within an ADRA1D multimer, and impart divergent pharmacological properties to the complex. Our results reveal an unprecedented modular dimeric architecture for the ADRA1D in the cell membrane, providing unexpected opportunities for fine-tuning receptor function through novel protein interactions in vivo, and for intervening in signal transduction with small molecules that can stabilize or disrupt unique GPCR:PDZ protein interfaces. -
Hormonal Regulation of Oligodendrogenesis I: Effects Across the Lifespan
biomolecules Review Hormonal Regulation of Oligodendrogenesis I: Effects across the Lifespan Kimberly L. P. Long 1,*,†,‡ , Jocelyn M. Breton 1,‡,§ , Matthew K. Barraza 2 , Olga S. Perloff 3 and Daniela Kaufer 1,4,5 1 Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA; [email protected] (J.M.B.); [email protected] (D.K.) 2 Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720, USA; [email protected] 3 Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94143, USA; [email protected] 4 Department of Integrative Biology, University of California, Berkeley, CA 94720, USA 5 Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada * Correspondence: [email protected] † Current address: Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA 94143, USA. ‡ These authors contributed equally to this work. § Current address: Department of Psychiatry, Columbia University, New York, NY 10027, USA. Abstract: The brain’s capacity to respond to changing environments via hormonal signaling is critical to fine-tuned function. An emerging body of literature highlights a role for myelin plasticity as a prominent type of experience-dependent plasticity in the adult brain. Myelin plasticity is driven by oligodendrocytes (OLs) and their precursor cells (OPCs). OPC differentiation regulates the trajectory of myelin production throughout development, and importantly, OPCs maintain the ability to proliferate and generate new OLs throughout adulthood. The process of oligodendrogenesis, Citation: Long, K.L.P.; Breton, J.M.; the‘creation of new OLs, can be dramatically influenced during early development and in adulthood Barraza, M.K.; Perloff, O.S.; Kaufer, D.