DOCSLIB.ORG

Expression and Possible Role of Fibroblast Growth Factor Family

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Expression and Possible Role of Fibroblast Growth Factor Family REPRODUCTIONRESEARCH Expression of mRNA for galanin, galanin-like peptide and galanin receptors 1–3 in the ovine hypothalamus and pituitary gland: effects of age and gender Christine Margaret Whitelaw, Jane Elizabeth Robinson, George Ballantine Chambers, Peter Hastie, Vasantha Padmanabhan1, Robert Charles Thompson1 and Neil Price Evans Division of Cell Sciences, Faculty of Veterinary Medicine, Institute of Comparative Medicine, University of Glasgow, Glasgow G61 1QH, UK and 1Department of Pediatrics and Psychiatry, University of Michigan, Ann Arbor, Michigan 48103, USA Correspondence should be addressed to N P Evans; Email: [email protected] Abstract The neurotransmitters/neuromodulators galanin (GAL) and galanin-like peptide (GALP) are known to operate through three G protein- coupled receptors, GALR1, GALR2 and GALR3. The aim of this study was to investigate changes in expression of mRNA for galanin, GALP and GALR1–3 in the hypothalamus and pituitary gland, of male and female sheep, to determine how expression changed in association with growth and the attainment of reproductive competence. Tissue samples from the hypothalami and pituitary glands were analysed from late foetal and pre-pubertal lambs and adult sheep. Although mRNA for galanin and GALR1-3 was present in both tissues, at all ages and in both genders, quantification of GALP mRNA was not possible due to its low levels of expression. mRNA expression for both galanin and its receptors was seen to change significantly in both tissues as a function of age. Specifically, hypothalamic galanin mRNA expression increased with age in the male, but decreased with age in the female pituitary gland. mRNA expression for all receptors increased between foetal and pre-pubertal age groups and decreased significantly between pre-pubertal and adult animals. The results indicate that the expression of mRNA for galanin and its receptors changes dynamically with age and those significant differences exist with regard to tissue type and gender. These changes suggest that galaninergic neuroendocrine systems could be involved in the regulation of ovine growth and or the development of reproductive competence. The roles played by these systems in the sheep, however, may differ from other species, in particular the neuroendocrine link between nutrition and reproduction and GALR1’s role in pituitary signalling. Reproduction (2009) 137 141–150 Introduction three G protein-coupled receptors; galanin receptor 1 (GALR1), galanin receptor 2 (GALR2) and galanin Galanin was initially isolated from porcine gut, and the receptor 3 (GALR3). mRNA for each receptor isoform expression of this 29 amino acid peptide has since been has been reported in numerous peripheral tissues, in a reported in a variety of species and tissues, including the variety of species (Urbanski & Ojeda 1990, Bartfai et al. central and peripheral nervous systems (Melander et al. 1993, Lorimer & Benya 1996, Wang et al. 1997). In 1986, Skofitsch & Jacobowitz 1986, Chaillou et al. addition, the receptor mRNA has been reported to be 1999). Due to its widespread distribution within the expressed within developing neural tissue (Tarasov et al. central nervous system (CNS), it has been proposed that 2002) and within the adult CNS (Waters & Krause 2000). galanin is involved in the regulation of a number of In addition to galanin, the endogenous peptide physiological processes, including nutrition, growth and galanin-like peptide (GALP) is also able to activate reproduction (Crawley et al. 1993, Cheung et al. 1996, galanin receptors. GALP is a 60 amino acid peptide, Baratta et al. 1997, Shen et al. 1998, Chaillou & Tillet originally isolated from porcine hypothalamic extracts 2005). Reported changes in galanin expression during (Ohtaki et al. 1999). GALP has a high structural foetal and post-natal development in the rat, human and homology with galanin (Ohtaki et al. 1999, Cunningham opossum also suggest that galanin may be involved in the et al. 2002) and is able to bind to all three receptor developmental differentiation of the foetal brain (Sizer isoforms. The greatest binding affinity being with GALR3 et al. 1990, Elmquist et al. 1992, Bhide & Puranik 2005). and the lowest with GALR1 (Lang et al. 2005). Galanin is highly conserved across species (Smith GALP-immunopositive cells exhibit a more limited et al. 1998) and is able to bind to and activate at least distribution within the hypothalamo-pituitary axis q 2009 Society for Reproduction and Fertility DOI: 10.1530/REP-08-0266 ISSN 1470–1626 (paper) 1741–7899 (online) Online version via www.reproduction-online.org Downloaded from Bioscientifica.com at 09/28/2021 04:17:06AM via free access 142 C M Whitelaw and others (Ohtaki et al. 1999) and species-specific differences be present within the ovine hypothalamus and a have been reported (Larm & Gundlach 2000, Jureus et al. proportion of the GALR2-immunopositive cells have 2001, Takatsu et al. 2001, Cunningham et al. 2002, been reported to be oestradiol sensitive (Chambers et al. Iqbal et al. 2005). 2007). However, to date, no studies have characterised A number of experimental observations have age-related changes in mRNA expression for galanin and suggested that galanin is particularly important in the its three receptor isoforms in the hypothalamo-pituitary regulation of growth and reproduction with studies axis of both male and female animals. showing galanin and its receptors co-expressed within Given the differences in the steroidogenic regulation both hypothalamic GnRH1 and GHRH neurones of GnRH1 secretion in mammals such as sheep and (Murakami et al. 1989, Hohmann et al. 1998). In humans, compared with rodents (Freeman 1993), and addition, hypothalamic galanin mRNA expression has the detailed knowledge of the effects of steroids on the been reported to increase with age through the juvenile patterns of ovine hypothalamic GnRH1 secretion (Clarke period, reaching a peak during puberty, in GnRH1 and et al. 1987, Moenter et al. 1992, 1993, Evans et al. other hypothalamic neurones of both male and female 1995a, 1995b, Skinner et al. 1998), this study aimed to rats (Planas et al. 1994, 1995, Rossmanith et al. 1994). increase our understanding of age-related changes in The number of galaninergic synapses onto GnRH1 hypothalamo-pituitary galanin, GALP and GALR mRNA neuronal cell bodies has also been reported to be expression, in male and female sheep. increased in adult, compared with juvenile female mice The approach used in this study was to quantify the (Rajendren & Li 2001). expression of mRNA for GALP, galanin and its three Support for a specific role for galaninergic systems in receptor subtypes in the hypothalamus and pituitary the steroidogenic control of the reproductive and growth gland of late foetal, pre-pubertal and adult male and axes comes from the observation that many of the female sheep. To facilitate this work, partial mRNA reported developmental changes in galanin expression sequences for ovine galanin, GALP, GALR1, GALR2 and are gonad dependent (Rossmanith et al. 1994). In GALR3 were identified using RTPCR with primers addition, it has been reported that galanin expression designed against the conserved regions of published in both the hypothalamus and pituitary gland is sexually rat, mouse and human sequences. dimorphic, with higher levels of expression within the hypothalamus and specifically within hypothalamic GnRH1 neurones of female compared with male rats Results (Mitchell et al. 1999, Todman et al. 2005). The reported mRNA sequences for ovine galanin, GALP, GALR1, sexually dimorphic patterns of hypothalamic galanin GALR2 and GALR3 expression are of particular interest with regard to the steroidogenic regulation of GnRH1 secretion, as they Partial mRNA sequences were obtained and published mean that galanin could be one of the neurotransmitter on the GenBank database, for ovine galanin (EF192581, systems involved in mediating the indirect, positive 290 bp), GALP (EF192585, 114 bp), GALR1 (EF192582, feedback effects of high concentrations of oestradiol on 208 bp), GALR2 (EF192583, 100 bp) and GALR3 GnRH1 neurones (Herbison et al. 1993, Lehman & (EF192584, 196 bp). The mRNA sequence for ovine Karsch 1993, Evans et al. 1997, Skinner et al. 2001). galanin encompasses that which encodes the secreted There is also evidence to suggest that GALP could be peptide. Those obtained for the three receptors only involved with the regulation of reproduction, as GALP- encoded that part of the predicted amino acid sequence positive fibres have been shown to make contact with that could be identified specifically for each receptor, to GnRH1 cell bodies (Takatsu et al. 2001). In addition, enable design of specific ovine qPCR primers and probes intracerebroventricular injections of GALP have been for the three galanin receptor isoforms. The mRNA shown to stimulate fos activity in GnRH1 neurones, and sequences identified, all showed high homology with subsequent LH secretion, via an action within the those reported in other species: galanin, bovine 98%, hypothalamus that can be blocked with the competitive porcine 90% and murine 89%; GALR1, equine 94%, GnRH1 antagonist, cetrorelix (Matsumoto et al. 2001). murine 93% and human 90%; GALR2, rat 89%, murine Previous studies in sheep have reported that galanin is 89% and human 89%; GALR3, bovine 97%, human expressed within the hypothalamus and pituitary gland 90% and murine 85%; and GALP, murine 96%, human (Tempel et al. 1988, Leibowitz et al. 1998, Chaillou et al. 82% and rat 100%. 1999),
Load more

Recommended publications
  • Bone-Specific Master Transcription Factor Runx2 Regulates Signaling and Metabolism Related Programs in Osteoprogenitors
    ISSN 0233-7657. Biopolymers and Cell. 2010. Vol. 26. N 4 Bone-specific master transcription factor Runx2 regulates signaling and metabolism related programs in osteoprogenitors N. M. Teplyuk1, 2, V. I. Teplyuk2 1University of Massachusetts Medical School 55, Lake Ave North, 01655, Worcester, MA, USA 2Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine 150, Zabolotnogo str., Kiev, Ukraine, 03680 [email protected] Aim. Runx2 (AML3) transcription factor is the key regulator of osteoblastic lineage progression and is indispensable for the formation of mineral bones. Runx2 expression increases during differentiation of osteoblasts to induce osteoblast-specific genes necessary for the production and deposition of bone mineral matrix. However, Runx2 is also expressed at a lower level in early osteoprogenitors, where its function is less understood. Here we study how Runx2 determines the early stages of osteoblastic commitment using the model system of Runx2 re-introduction in mouse calvaria cells with Runx2 null background. Method. Affymetrix analysis, Western blot analysis and quantitative real-time reverse transcriptase PCR (qRT-PCR) analysis were employed. Results. Gene expression profiling by Affymetrix microarrays revealed that along with the induction of extracellular matrix and bone mineral deposition related phenotypic markers, Runx2 regulates several cell programs related to signaling and metabolism in the early osteoprogenitors. Particularly, Runx2 regulates transcription of genes involved in G-protein coupled signaling network, FGF and BMP/TGF beta signaling pathways and in biogenesis and metabolism pathways of steroid hormones. Conclusion. The data indicate that the lineage specific program, regulated by the master regulatory transcription factor, includes the regulation of cellular signaling and metabolism which may allow the committed cell to react and behave differently in the same microenvironment.
    [Show full text]
  • Galanin Stimulates Cortisol Secretion from Human Adrenocortical Cells
    859-864 9/11/07 11:36 Page 859 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 20: 859-864, 2007 859 Galanin stimulates cortisol secretion from human adrenocortical cells through the activation of galanin receptor subtype 1 coupled to the adenylate cyclase-dependent signaling cascade ANNA S. BELLONI1, LUDWIK K. MALENDOWICZ2, MARCIN RUCINSKI2, DIEGO GUIDOLIN1 and GASTONE G. NUSSDORFER1 1Department of Human Anatomy and Physiology, School of Medicine, University of Padua, I-35121 Padua, Italy; 2Department of Histology and Embryology, Poznan School of Medicine, PL-60781 Poznan, Poland Received September 10, 2007; Accepted October 5, 2007 Abstract. Previous studies showed that galanin receptors are Introduction expressed in the rat adrenal, and galanin modulates gluco- corticoid secretion in this species. Hence, we investigated the Galanin is a regulatory peptide (30 amino acid residues in expression of the various galanin receptor subtypes (GAL-R1, humans) originally isolated from pig intestine (1) which is GAL-R2 and GAL-R3) in the human adrenocortical cells, and widely distributed in the central and peripheral nervous the possible involvement of galanin in the control of cortisol system, where it acts as a neurotransmitter/neuromodulator. secretion. Reverse transcription-polymerase chain reaction In the gut, galanin modulates insulin release and intestine detected the expression of GAL-R1 (but not GAL-R2 and contractility (2,3). Galanin acts through three distinct subtypes GAL-R3) in the inner zones of the human adrenal cortex. The of G protein-coupled receptors, referred to as GAL-R1, GAL-R2 galanin concentration dependently enhanced basal, but not and GAL-R3 (4). ACTH-stimulated secretion of cortisol from dispersed inner Evidence suggests that galanin is involved in the functional adrenocortical cells (maximal effective concentration, 10-8 M).
    [Show full text]
  • Characterization of a High-Affinity Galanin Receptor in the Rat
    Proc. Natl. Acad. Sci. USA Vol. 90, pp. 4231-4235, May 1993 Neurobiology Characterization of a high-affinity galanin receptor in the rat anterior pituitary: Absence of biological effect and reduced membrane binding of the antagonist M15 differentiate it from the brain/gut receptor (galanin fragment/hemolytic plaque technique/prolactin) DAVID WYNICK*, DAVID M. SMITH*, MOHAMMAD GHATEI*, KAREN AKINSANYA*, RANJEV BHOGAL*, PAUL PURKISSt, PETER BYFIELDt, NOBORU YANAIHARAt, AND STEPHEN R. BLOOM* *Department of Medicine, Hammersmith Hospital, London W12 ONN, United Kingdom; tHaemostasis Research Group, Clinical Research Centre, Harrow, Middlesex, HAl 3UJ, United Kingdom; and tDepartment of Bio-organic Chemistry, University of Shizuoka, Shizuoka, Japan Communicated by L. L. Iversen, December 30, 1992 (received for review November 24, 1992) ABSTRACT Structure-activity studies demonstrate that anterior pituitary, where it has been shown to be estrogen galanin fragments 1-15 and 2-29 are fully active, whereas inducible (5). fragment 3-29 has been reported to be inactive, in a number Various studies have demonstrated effects of galanin on ofdifferent in vivo models. M15, a chimeric peptide comprising basal and stimulated release of prolactin (6, 7), growth galanin 1-13 and substance P 5-11, has recently been found to hormone (8-11), and luteinizing hormone (12, 13) either from be a potent galanin antagonist. Direct effects of galanin at the dispersed pituitary cells or at the hypothalamic level modu- level of the pituitary have been defined, yet, paradoxically, a lating dopamine, somatostatin (SRIF; somatotropin release- number of studies have been unable to demonstrate galanin inhibiting factor), and gonadotropin-releasing hormone binding to an anterior pituitary receptor.
    [Show full text]
  • Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes
    Tohoku J. Exp. Med., 2011,Differential 223, 161-176 Gene Expression in OPCs, Oligodendrocytes and Type II Astrocytes 161 Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes Jian-Guo Hu,1,2,* Yan-Xia Wang,3,* Jian-Sheng Zhou,2 Chang-Jie Chen,4 Feng-Chao Wang,1 Xing-Wu Li1 and He-Zuo Lü1,2 1Department of Clinical Laboratory Science, The First Affiliated Hospital of Bengbu Medical College, Bengbu, P.R. China 2Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, P.R. China 3Department of Neurobiology, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China 4Department of Laboratory Medicine, Bengbu Medical College, Bengbu, P.R. China Oligodendrocyte precursor cells (OPCs) are bipotential progenitor cells that can differentiate into myelin-forming oligodendrocytes or functionally undetermined type II astrocytes. Transplantation of OPCs is an attractive therapy for demyelinating diseases. However, due to their bipotential differentiation potential, the majority of OPCs differentiate into astrocytes at transplanted sites. It is therefore important to understand the molecular mechanisms that regulate the transition from OPCs to oligodendrocytes or astrocytes. In this study, we isolated OPCs from the spinal cords of rat embryos (16 days old) and induced them to differentiate into oligodendrocytes or type II astrocytes in the absence or presence of 10% fetal bovine serum, respectively. RNAs were extracted from each cell population and hybridized to GeneChip with 28,700 rat genes. Using the criterion of fold change > 4 in the expression level, we identified 83 genes that were up-regulated and 89 genes that were down-regulated in oligodendrocytes, and 92 genes that were up-regulated and 86 that were down-regulated in type II astrocytes compared with OPCs.
    [Show full text]
  • Identification of a Novel Synaptic G Protein-Coupled Receptor Controlling Nicotine Dependence and Withdrawal
    Identification of a novel synaptic G protein-coupled receptor controlling nicotine dependence and withdrawal Inaugural-Dissertation to obtain the academic degree Doctor rerum naturalium (Dr. rer. nat.) Submitted to the Department of Biology, Chemistry and Pharmacy of the Freie Universität Berlin by Beatriz Antolin Fontes from Girona, Spain Berlin, March 2014 This work was carried out in the period from June 2010 until March 2014 under the supervision of Dr. Inés Ibañez-Tallon and Prof. Dr. Constance Scharff at the Max- Delbrück-Center for Molecular Medicine (MDC) in Berlin and at The Rockefeller University in New York. 1st Reviewer: Dr. Inés Ibañez-Tallon 2nd Reviewer: Prof. Dr. Constance Scharff Date of defense: 18.06.2014 Scientific Acknowledgments I would like to express my sincere gratitude to all the people who made this thesis possible: - My supervisor Dr. Inés Ibañez-Tallon: For your advice, support and supervision throughout the years. Thank you for believing in me from the first moment, for giving me the opportunity to do research in different outstanding environments and specially, for transmitting always motivation and inspiration. I could not wish for a better supervisor. - My supervisor Prof. Dr. Constance Scharff from the Freie Universität Berlin: For your supervision and advice. - Prof. Dr. Nathaniel Heintz: For your valuable support and for so many useful and constructive recommendations on this project. - My fellow lab members, both current and past: Dr. Silke Frahm-Barske, Dr. Marta Slimak, Dr. Jessica Ables, Dr. Andreas Görlich, Dr. Sebastian Auer, Branka Kampfrath, Cuidong Wang, Syed Shehab, Dr. Martin Laqua, Dr. Julio Santos-Torres, Susanne Wojtke, Monika Schwarz-Harsi, and all Prof.
    [Show full text]
  • Co-Regulation of Hormone Receptors, Neuropeptides, and Steroidogenic Enzymes 2 Across the Vertebrate Social Behavior Network 3 4 Brent M
    bioRxiv preprint doi: https://doi.org/10.1101/435024; this version posted October 4, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Co-regulation of hormone receptors, neuropeptides, and steroidogenic enzymes 2 across the vertebrate social behavior network 3 4 Brent M. Horton1, T. Brandt Ryder2, Ignacio T. Moore3, Christopher N. 5 Balakrishnan4,* 6 1Millersville University, Department of Biology 7 2Smithsonian Conservation Biology Institute, Migratory Bird Center 8 3Virginia Tech, Department of Biological Sciences 9 4East Carolina University, Department of Biology 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 1 bioRxiv preprint doi: https://doi.org/10.1101/435024; this version posted October 4, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Running Title: Gene expression in the social behavior network 2 Keywords: dominance, systems biology, songbird, territoriality, genome 3 Corresponding Author: 4 Christopher Balakrishnan 5 East Carolina University 6 Department of Biology 7 Howell Science Complex 8 Greenville, NC, USA 27858 9 [email protected] 10 2 bioRxiv preprint doi: https://doi.org/10.1101/435024; this version posted October 4, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
    [Show full text]
  • Design, Synthesis and Characterization of Galanin Receptor Selective Ligands
    !" #$"% "!&$$ ' () * ( +",-& . #/0!$ !$ 1 &2 . &2 "3 ( &. 4 . ( ( ( . &5 ( &6 ( ( 4 ( ( 4 & 0 & ( & 2 & " # (3 7#""8&9 (. : 4 4 & # 4 4 "& ( . : & ! # : & ; &7!/<8 4 & 9 ( ( & !" #$"% =00 && 0 > ? == = = "!/@@$ 9-/%@/"%,;/%#"$ 9-/%@/"%,;/%##% # $% # ("$,/" Design, Synthesis and Characterization of Galanin Receptor Selective Ligands Kristin Webling Abstract Galanin is a 29/30 amino acid long bioactive peptide discovered over 30 years ago when C-terminally amidated peptides were isolated from porcine intestines. The name galanin originates from a combination of the first and last amino acids - G from glycine and the rest from alanine. The first 15 amino acids are highly conserved throughout species, which indicates that the N-terminus is important for receptor recognition and binding. Galanin exerts its effects by binding to three different G protein-coupled receptors, which all differ according to regional distribution,
    [Show full text]
  • The Second Galanin Receptor Galr2 Plays a Key Role in Neurite Outgrowth from Adult Sensory Neurons
    416 • The Journal of Neuroscience, January 15, 2003 • 23(2):416–421 The Second Galanin Receptor GalR2 Plays a Key Role in Neurite Outgrowth from Adult Sensory Neurons Sally-Ann Mahoney,1 Richard Hosking,1 Sarah Farrant,1 Fiona E. Holmes,1 Arie S. Jacoby,2 John Shine,2 Tiina P. Iismaa,2 Malcolm K. Scott,3 Ralf Schmidt,4 and David Wynick1 1University Research Centre for Neuroendocrinology, Bristol University, Bristol BS2 8HW, United Kingdom, 2The Garvan Institute of Medical Research, Sydney, NSW 2010, Australia, 3Johnson & Johnson Pharmaceutical Research Institute, Spring House, Pennsylvania 19477-0776, and 4AstraZeneca R&D Montreal, Montreal, Quebec H4S 1Z9, Canada Expression of the neuropeptide galanin is markedly upregulated within the adult dorsal root ganglion (DRG) after peripheral nerve injury. We demonstrated previously that the rate of peripheral nerve regeneration is reduced in galanin knock-out mice, with similar deficits observed in neurite outgrowth from cultured mutant DRG neurons. Here, we show that the addition of galanin peptide signifi- cantly enhanced neurite outgrowth from wild-type sensory neurons and fully rescued the observed deficits in mutant cultures. Further- more,neuriteoutgrowthinwild-typecultureswasreducedtolevelsobservedinthemutantsbytheadditionofthegalaninantagonistM35 [galanin(1–13)bradykinin(2–9)]. Study of the first galanin receptor (GalR1) knock-out animals demonstrated no differences in neurite outgrowth compared with wild-type animals. Similarly, use of a GalR1-specific antagonist had no effect on neuritogenesis. In contrast, use of a GalR2-specific agonist had equipotent effects on neuritogenesis to galanin peptide, and inhibition of PKC reduced neurite outgrowth from wild-type sensory neurons to that observed in galanin knock-out cultures.
    [Show full text]
  • New Insights Into Metabolic Homeostasis Keith Tan
    Rockefeller University Digital Commons @ RU Student Theses and Dissertations 2015 Activity Based Profiling: New Insights into Metabolic Homeostasis Keith Tan Follow this and additional works at: http://digitalcommons.rockefeller.edu/ student_theses_and_dissertations Part of the Life Sciences Commons Recommended Citation Tan, Keith, "Activity Based Profiling: New Insights into Metabolic Homeostasis" (2015). Student Theses and Dissertations. Paper 285. This Thesis is brought to you for free and open access by Digital Commons @ RU. It has been accepted for inclusion in Student Theses and Dissertations by an authorized administrator of Digital Commons @ RU. For more information, please contact [email protected]. ACTIVITY BASED PROFILING: NEW INSIGHTS INTO METABOLIC HOMEOSTASIS A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy by Keith Tan June 2015 © Copyright by Keith Tan 2015 ACTIVITY BASED PROFILING: NEW INSIGHTS INTO METABOLIC HOMEOSTASIS Keith Tan, Ph.D. The Rockefeller University 2015 There is mounting evidence that demonstrates that body weight and energy homeostasis is tightly regulated by a physiological system. This system consists of sensing and effector components that primarily reside in the central nervous system and disruption to these components can lead to obesity and metabolic disorders. Although many neural substrates have been identified in the past decades, there is reason to believe that there are numerous unidentified neural populations that play a role in energy balance. Besides regulating caloric consumption and energy expenditure, neural components that control energy homeostasis are also tightly intertwined with circadian rhythmicity but this aspect has received less attention.
    [Show full text]
  • The G Protein-Coupled Receptor Heterodimer Network (GPCR-Hetnet) and Its Hub Components
    Int. J. Mol. Sci. 2014, 15, 8570-8590; doi:10.3390/ijms15058570 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Article The G Protein-Coupled Receptor Heterodimer Network (GPCR-HetNet) and Its Hub Components Dasiel O. Borroto-Escuela 1,†,*, Ismel Brito 1,2,†, Wilber Romero-Fernandez 1, Michael Di Palma 1,3, Julia Oflijan 4, Kamila Skieterska 5, Jolien Duchou 5, Kathleen Van Craenenbroeck 5, Diana Suárez-Boomgaard 6, Alicia Rivera 6, Diego Guidolin 7, Luigi F. Agnati 1 and Kjell Fuxe 1,* 1 Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden; E-Mails: [email protected] (I.B.); [email protected] (W.R.-F.); [email protected] (M.D.P.); [email protected] (L.F.A.) 2 IIIA-CSIC, Artificial Intelligence Research Institute, Spanish National Research Council, 08193 Barcelona, Spain 3 Department of Earth, Life and Environmental Sciences, Section of Physiology, Campus Scientifico Enrico Mattei, Urbino 61029, Italy 4 Department of Physiology, Faculty of Medicine, University of Tartu, Tartu 50411, Estonia; E-Mail: [email protected] 5 Laboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Ghent University, 9000 Ghent, Belgium; E-Mails: [email protected] (K.S.); [email protected] (J.D.); [email protected] (K.V.C.) 6 Department of Cell Biology, School of Science, University of Málaga, 29071 Málaga, Spain; E-Mails: [email protected] (D.S.-B.); [email protected] (A.R.) 7 Department of Molecular Medicine, University of Padova, Padova 35121, Italy; E-Mail: [email protected] † These authors contributed equally to this work.
    [Show full text]
  • Hypothetical Orchestrated Cooperation Between Dopaminergic and Kinin Receptors for the Regulation of Common Functions*
    Vol. 63, No 3/2016 387–396 http://dx.doi.org/10.18388/abp.2016_1366 Review Hypothetical orchestrated cooperation between dopaminergic and kinin receptors for the regulation of common functions* Ibeth Guevara-Lora1*, Anna Niewiarowska-Sendo1, Agnieszka Polit2 and Andrzej Kozik1 1Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Kraków, Poland; 2Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Kraków, Poland The G protein-coupled receptors (GPCRs), one of the tor molecules that form homodimers, heterodimers, or largest protein families, are essential components of high-ordered oligomers can be distinguished (Thomsen the most commonly used signal-transduction systems in et al., 2005; Milligan, 2009; Tadagaki et al., 2012). Dif- cells. These receptors, often using common pathways, ferent types of GPCR assembly have been proposed, may cooperate in the regulation of signal transmission including disulphide bond formation at the N-terminal to the cell nucleus. Recent scientific interests increas- tails, coiled-coil interaction at the C-terminal tails, and ingly focus on the cooperation between these receptors, direct interactions between transmembrane helices (Bou- particularly in a context of their oligomerization, e.g. the vier, 2001). The formation of GPCR oligomers has been formation of dimers that are able to change characteris- widely demonstrated using different techniques, e.g., tic signaling of each receptor. Numerous studies on kinin co-immunoprecipitation, bioluminescent resonance en- and dopamine receptors which belong to this family of ergy transfer, fluorescent resonance energy transfer, and receptors have shown new facts demonstrating their proximity ligation assay (Thomsen et al., 2005).
    [Show full text]
  • The Galanin Receptor Type 2 Initiates Multiple Signaling Pathways in Small Cell Lung Cancer Cells by Coupling to Gq, Gi And
    Oncogene (2000) 19, 4199 ± 4209 ã 2000 Macmillan Publishers Ltd All rights reserved 0950 ± 9232/00 $15.00 www.nature.com/onc The galanin receptor type 2 initiates multiple signaling pathways in small cell lung cancer cells by coupling to Gq,Gi and G12 proteins Norbert Wittau1, Robert Grosse1, Frank Kalkbrenner1,3, Antje Gohla1,GuÈ nter Schultz1 and Thomas Gudermann*,2 1Institut fuÈr Pharmakologie, UniversitaÈtsklinikum Benjamin Franklin, Freie UniversitaÈt Berlin, 14195 Berlin, Germany; 2Institut fuÈr Pharmakologie und Toxikologie, Fachbereich Humanmedizin, Philipps-UniversitaÈt Marburg, Karl-von-Frisch-Str. 1, 35033 Marburg, Germany Neuropeptides like galanin produced and released by mutations or overexpression of receptor tyrosine small cell lung cancer (SCLC) cells are considered kinases are usually not encountered in SCLC, and the principal mitogens in these tumors. We identi®ed the expression of GTPase-de®cient Ras mutants or of a galanin receptor type 2 (GALR2) as the only galanin constitutively active Raf kinase induces growth arrest receptor expressed in H69 and H510 cells. Photoanity and apoptosis (Dhanasekaran et al., 1995; Ravi et al., labeling of G proteins in H69 cell membranes revealed 1998). These ®ndings lend credibility to the belief that that GALR2 activates G proteins of three subfamilies: the main driving force for growth and proliferation of 2+ Gq,Gi, and G12. In H69 cells, galanin-induced Ca this subtype of cancer is represented by various mobilization was pertussis toxin-insensitive. While neuropeptides, e.g. bombesin/gastrin-releasing peptide phorbol ester-induced extracellular signal-regulated ki- (GRP), bradykinin, cholecystokinin, gastrin, neuroten- nase (ERK) activation required protein kinase C (PKC) sin, vasopressin and galanin which stimulate SCLC cells activity, preincubation of H69 cells with the PKC- via multiple auto- and paracrine loops (Rozengurt, inhibitor GF109203X had no eect on galanin-dependent 1999).
    [Show full text]