Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 24 October 1997:
Vol. 278. no. 5338, pp. 698 - 701
DOI: 10.1126/science.278.5338.698
Prev | Table of Contents | Next

Reports

Fyn-Kinase as a Determinant of Ethanol Sensitivity: Relation to NMDA-Receptor Function

Tsuyoshi Miyakawa, * Takeshi Yagi, * Hiromasa Kitazawa, Masahiro Yasuda, Nobufumi Kawai, Kenta Tsuboi, Hiroaki Niki dagger

Animals vary in their sensitivity to ethanol, a trait at least partly determined by genetic factors. In order to identify possible responsible genes, mice lacking Fyn, a non-receptor type tyrosine kinase, were investigated. These mice were hypersensitive to the hypnotic effect of ethanol. The administration of ethanol enhanced tyrosine phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) in the hippocampus of control mice but not in Fyn-deficient mice. An acute tolerance to ethanol inhibition of NMDAR-mediated excitatory postsynaptic potentials in hippocampal slices developed in control mice but not in Fyn-deficient mice. These results indicate that Fyn affects behavioral, biochemical, and physiological responses to ethanol.

T. Miyakawa and H. Niki, Laboratory for Neurobiology of Emotion, Brain Science Institute, RIKEN, Hirosawa, Wako-shi, Saitama-ken 351-01, Japan.
T. Yagi and M. Yasuda, Laboratory of Neurobiology and Behavioral Genetics, National Institute for Physiological Sciences, Myodaiji, Okazaki 444, Japan.
H. Kitazawa and N. Kawai, Department of Physiology, Jichi Medical School, Minamikawachi-machi, Tochigi-ken 329-04, Japan.
K. Tsuboi, Department of Psychology, Faculty of Letters, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113, Japan.
*   These authors equally contributed to the biochemical findings.

dagger    To whom correspondence should be addressed.

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Tyrosine Phosphorylation of the 2B Subunit of the NMDA Receptor Is Necessary for Taste Memory Formation.
L. Barki-Harrington, A. Elkobi, T. Tzabary, and K. Rosenblum (2009)
J. Neurosci. 29, 9219-9226
   Abstract »    Full Text »    PDF »
Genetics of addictions: strategies for addressing heterogeneity and polygenicity of substance use disorders.
C. C.Y Wong and G. Schumann (2008)
Phil Trans R Soc B 363, 3213-3222
   Abstract »    Full Text »    PDF »
Systematic Analysis of Glutamatergic Neurotransmission Genes in Alcohol Dependence and Adolescent Risky Drinking Behavior.
G. Schumann, M. Johann, J. Frank, U. Preuss, N. Dahmen, M. Laucht, M. Rietschel, D. Rujescu, A. Lourdusamy, T.-K. Clarke, et al. (2008)
Arch Gen Psychiatry 65, 826-838
   Abstract »    Full Text »    PDF »
Mind Bomb-2 Is an E3 Ligase That Ubiquitinates the N-Methyl-D-aspartate Receptor NR2B Subunit in a Phosphorylation-dependent Manner.
R. Jurd, C. Thornton, J. Wang, K. Luong, K. Phamluong, V. Kharazia, S. L. Gibb, and D. Ron (2008)
J. Biol. Chem. 283, 301-310
   Abstract »    Full Text »    PDF »
Fyn-mediated Phosphorylation of NR2B Tyr-1336 Controls Calpain-mediated NR2B Cleavage in Neurons and Heterologous Systems.
H.-Y. Wu, F.-C. Hsu, A. J. Gleichman, I. Baconguis, D. A. Coulter, and D. R. Lynch (2007)
J. Biol. Chem. 282, 20075-20087
   Abstract »    Full Text »    PDF »
Ethanol Inhibits Persistent Activity in Prefrontal Cortical Neurons.
Y. Tu, S. Kroener, K. Abernathy, C. Lapish, J. Seamans, L. J. Chandler, and J. J. Woodward (2007)
J. Neurosci. 27, 4765-4775
   Abstract »    Full Text »    PDF »
The Novel Cellular Mechanism of Human 5-HT6 Receptor through an Interaction with Fyn.
H.-M. Yun, S. Kim, H.-J. Kim, E. Kostenis, J. I. Kim, J. Y. Seong, J.-H. Baik, and H. Rhim (2007)
J. Biol. Chem. 282, 5496-5505
   Abstract »    Full Text »    PDF »
Physical and Functional Interaction of Fyn Tyrosine Kinase with a Brain-enriched Rho GTPase-activating Protein TCGAP.
H. Liu, T. Nakazawa, T. Tezuka, and T. Yamamoto (2006)
J. Biol. Chem. 281, 23611-23619
   Abstract »    Full Text »    PDF »
Ethanol-Induced Hypnotic Tolerance Is Absent in N-Methyl-d-Aspartate Receptor {varepsilon}1 Subunit Knockout Mice..
Y. Sato, N. Seo, and E. Kobayashi (2006)
Anesth. Analg. 103, 117-120
   Abstract »    Full Text »    PDF »
Ethanol inhibits clearance of brain serotonin by a serotonin transporter-independent mechanism..
L. C. Daws, S. Montanez, J. L. Munn, W. A. Owens, N. L. Baganz, J. M. Boyce-Rustay, R. A. Millstein, L. M. Wiedholz, D. L. Murphy, and A. Holmes (2006)
J. Neurosci. 26, 6431-6438
   Abstract »    Full Text »    PDF »
Fyn Is Required for Haloperidol-induced Catalepsy in Mice.
K. Hattori, S. Uchino, T. Isosaka, M. Maekawa, M. Iyo, T. Sato, S. Kohsaka, T. Yagi, and S. Yuasa (2006)
J. Biol. Chem. 281, 7129-7135
   Abstract »    Full Text »    PDF »
Alcohol Potently Modulates Climbing Fiber->Purkinje Neuron Synapses: Role of Metabotropic Glutamate Receptors.
M. Carta, M. Mameli, and C. F. Valenzuela (2006)
J. Neurosci. 26, 1906-1912
   Abstract »    Full Text »    PDF »
Functional Dissection of Reelin Signaling by Site-Directed Disruption of Disabled-1 Adaptor Binding to Apolipoprotein E Receptor 2: Distinct Roles in Development and Synaptic Plasticity.
U. Beffert, A. Durudas, E. J. Weeber, P. C. Stolt, K. M. Giehl, J. D. Sweatt, R. E. Hammer, and J. Herz (2006)
J. Neurosci. 26, 2041-2052
   Abstract »    Full Text »    PDF »
The "Ups and Downs" of Signaling Cascades in Addiction.
D. Ron and R. Jurd (2005)
Sci. STKE 2005, re14
   Abstract »    Full Text »    PDF »
Absence of Fyn and Src Causes a Reeler-Like Phenotype.
G. Kuo, L. Arnaud, P. Kronstad-O'Brien, and J. A. Cooper (2005)
J. Neurosci. 25, 8578-8586
   Abstract »    Full Text »    PDF »
Ethanol Alters Trafficking and Functional N-Methyl-D-aspartate Receptor NR2 Subunit Ratio via H-Ras.
N. Suvarna, S. L. Borgland, J. Wang, K. Phamluong, Y. P. Auberson, A. Bonci, and D. Ron (2005)
J. Biol. Chem. 280, 31450-31459
   Abstract »    Full Text »    PDF »
Developmentally Regulated Actions of Alcohol on Hippocampal Glutamatergic Transmission.
M. Mameli, P. A. Zamudio, M. Carta, and C. F. Valenzuela (2005)
J. Neurosci. 25, 8027-8036
   Abstract »    Full Text »    PDF »
From The Cover: Ethanol-withdrawal seizures are controlled by tissue plasminogen activator via modulation of NR2B-containing NMDA receptors.
R. Pawlak, J. P. Melchor, T. Matys, A. E. Skrzypiec, and S. Strickland (2005)
PNAS 102, 443-448
   Abstract »    Full Text »    PDF »
Depolarization Activates ERK and Proline-rich Tyrosine Kinase 2 (PYK2) Independently in Different Cellular Compartments in Hippocampal Slices.
J.-C. Corvol, E. Valjent, M. Toutant, H. Enslen, T. Irinopoulou, S. Lev, D. Herve, and J.-A. Girault (2005)
J. Biol. Chem. 280, 660-668
   Abstract »    Full Text »    PDF »
Chronic Ethanol Induces Synaptic But Not Extrasynaptic Targeting of NMDA Receptors.
E. P. Carpenter-Hyland, J. J. Woodward, and L. J. Chandler (2004)
J. Neurosci. 24, 7859-7868
   Abstract »    Full Text »    PDF »
Signaling Cascades Regulating NMDA Receptor Sensitivity to Ethanol.
D. Ron (2004)
Neuroscientist 10, 325-336
   Abstract »    PDF »
Ethanol, Fruit Ripening, and the Historical Origins of Human Alcoholism in Primate Frugivory.
R. Dudley (2004)
Integr. Comp. Biol. 44, 315-323
   Abstract »    Full Text »    PDF »
Tyrosine Phosphorylation and Regulation of the AMPA Receptor by Src Family Tyrosine Kinases.
T. Hayashi and R. L. Huganir (2004)
J. Neurosci. 24, 6152-6160
   Abstract »    Full Text »    PDF »
Deletion of the fyn-Kinase Gene Alters Sensitivity to GABAergic Drugs: Dependence on {beta}2/{beta}3 GABAA Receptor Subunits.
S. L. Boehm II, L. Peden, R. A. Harris, and Y. A. Blednov (2004)
J. Pharmacol. Exp. Ther. 309, 1154-1159
   Abstract »    Full Text »    PDF »
Selective Breeding, Quantitative Trait Locus Analysis, and Gene Arrays Identify Candidate Genes for Complex Drug-Related Behaviors.
B. Tabakoff, S. V. Bhave, and P. L. Hoffman (2003)
J. Neurosci. 23, 4491-4498
   Abstract »    Full Text »    PDF »
Scaffolding of Fyn Kinase to the NMDA Receptor Determines Brain Region Sensitivity to Ethanol.
R. Yaka, K. Phamluong, and D. Ron (2003)
J. Neurosci. 23, 3623-3632
   Abstract »    Full Text »    PDF »
Tyrosine Dephosphorylation and Ethanol Inhibition of N-Methyl-D-aspartate Receptor Function.
R. M. Alvestad, D. R. Grosshans, S. J. Coultrap, T. Nakazawa, T. Yamamoto, and M. D. Browning (2003)
J. Biol. Chem. 278, 11020-11025
   Abstract »    Full Text »    PDF »
Ethanol Antagonizes Kainate Receptor-Mediated Inhibition of Evoked GABAA Inhibitory Postsynaptic Currents in the Rat Hippocampal CA1 Region.
T. L. Crowder, O. J. Ariwodola, and J. L. Weiner (2002)
J. Pharmacol. Exp. Ther. 303, 937-944
   Abstract »    Full Text »    PDF »
Novel Antagonists of Alcohol Inhibition of L1-Mediated Cell Adhesion: Multiple Mechanisms of Action.
M. F. Wilkemeyer, C. E. Menkari, and M. E. Charness (2002)
Mol. Pharmacol. 62, 1053-1060
   Abstract »    Full Text »    PDF »
Fyn Tyrosine Kinase in Sertoli Cells Is Involved in Mouse Spermatogenesis.
M. Maekawa, Y. Toyama, M. Yasuda, T. Yagi, and S. Yuasa (2002)
Biol Reprod 66, 211-221
   Abstract »    Full Text »
Interaction of the SH2 Domain of Fyn with a Cytoskeletal Protein, beta -Adducin.
T. Shima, N. Okumura, T. Takao, Y. Satomi, T. Yagi, M. Okada, and K. Nagai (2001)
J. Biol. Chem. 276, 42233-42240
   Abstract »    Full Text »    PDF »
A Unique Role for Fyn in CNS Myelination.
B. R. Sperber, E. A. Boyle-Walsh, M. J. Engleka, P. Gadue, A. C. Peterson, P. L. Stein, S. S. Scherer, and F. A. McMorris (2001)
J. Neurosci. 21, 2039-2047
   Abstract »    Full Text »    PDF »
Drugs of Abuse and Brain Gene Expression.
G. Torres and J. M. Horowitz (1999)
Psychosom Med 61, 630-650
   Abstract »    Full Text »    PDF »
Metabolic Deficiencies in Alcohol Dehydrogenase Adh1, Adh3, and Adh4 Null Mutant Mice. OVERLAPPING ROLES OF Adh1 AND Adh4 IN ETHANOL CLEARANCE AND METABOLISM OF RETINOL TO RETINOIC ACID.
L. Deltour, M. H. Foglio, and G. Duester (1999)
J. Biol. Chem. 274, 16796-16801
   Abstract »    Full Text »    PDF »
Growth factor-mediated Fyn signaling regulates alpha -amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor expression in rodent neocortical neurons.
M. Narisawa-Saito, A. J. Silva, T. Yamaguchi, T. Hayashi, T. Yamamoto, and H. Nawa (1999)
PNAS 96, 2461-2466
   Abstract »    Full Text »    PDF »
PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A.
T. Tezuka, H. Umemori, T. Akiyama, S. Nakanishi, and T. Yamamoto (1999)
PNAS 96, 435-440
   Abstract »    Full Text »    PDF »
N-Methyl-D-aspartate Inhibits Apoptosis through Activation of Phosphatidylinositol 3-Kinase in Cerebellar Granule Neurons. A ROLE FOR INSULIN RECEPTOR SUBSTRATE-1 IN THE NEUROTROPHIC ACTION OF N-METHYL-D-ASPARTATE AND ITS INHIBITION BY ETHANOL.
F. X. Zhang, R. Rubin, and T. A. Rooney (1998)
J. Biol. Chem. 273, 26596-26602
   Abstract »    Full Text »    PDF »
Protein Kinase Cdelta Mediates Ethanol-induced Up-regulation of L-type Calcium Channels.
E. H. Gerstin Jr., T. McMahon, J. Dadgar, and R. O. Messing (1998)
J. Biol. Chem. 273, 16409-16414
   Abstract »    Full Text »    PDF »
Glutamate Receptor-Mediated Hyperexcitability after Ethanol Exposure in Isolated Neonatal Rat Spinal Cord.
S. M. E. Wong, D. L. Tauck, E. G. Fong, and J. J. Kendig (1998)
J. Pharmacol. Exp. Ther. 285, 201-207
   Abstract »    Full Text »
Abnormal Synaptic Transmission in the Olfactory Bulb of Fyn-Kinase-Deficient Mice.
H. Kitazawa, T. Yagi, T. Miyakawa, H. Niki, and N. Kawai (1998)
J Neurophysiol 79, 137-142
   Abstract »    Full Text »    PDF »
Characterization of Fyn-mediated Tyrosine Phosphorylation Sites on GluRepsilon 2 (NR2B) Subunit of the N-Methyl-D-aspartate Receptor.
T. Nakazawa, S. Komai, T. Tezuka, C. Hisatsune, H. Umemori, K. Semba, M. Mishina, T. Manabe, and T. Yamamoto (2001)
J. Biol. Chem. 276, 693-699
   Abstract »    Full Text »    PDF »
Dual Role of Fyn in the Regulation of FAK+6,7 by Cannabinoids in Hippocampus.
P. Derkinderen, M. Toutant, G. Kadare, C. Ledent, M. Parmentier, and J.-A. Girault (2001)
J. Biol. Chem. 276, 38289-38296
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)