Cerebellar Granule Cell Migration and the Effects of AlcoholJiang Y.a · Kumada T.a · Cameron D.B.a · Komuro H.a, b
aDepartment of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, and bDepartment of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA
Dr. Hitoshi Komuro
Department of Neurosciences/NC30, Lerner Research Institute
The Cleveland Clinic Foundation, 9500 Euclid Avenue
Cleveland, OH 44195 (USA)
Tel. +1 216 444 4497, Fax +1 216 444 7927, E-Mail firstname.lastname@example.org
Do you have an account?
In the developing brain the majority of neurons migrate from their birthplace to their final destination. This active movement is essential for the formation of cortical layers and nuclei. The impairment of migration does not affect the viability of neurons but often results in abnormal differentiation. The proper migration of neurons requires the orchestrated activities of multiple cellular and molecular events, such as pathway selection, the activation of specific receptors and channels, and the assembly and disassembly of cytoskeletal components. The migration of neurons is very vulnerable to exposure to environmental toxins, such as alcohol. In this article, we will focus on recent developments in the migration of cerebellar granule cells. First, we will describe when, where and how granule cells migrate through different cortical layers to reach their final destination. Second, we will present how internal programs control the sequential changes in granule cell migration. Third, we will review the roles of external guidance cues and transmembrane signals in granule cell migration. Finally, we will reveal mechanisms by which alcohol exposure impairs granule cell migration.
© 2008 S. Karger AG, Basel
- Rakic P: Principles of neuronal cell migration. Experientia 1990;46:882–891.
- Hatten ME, Heintz N: Mechanisms of neural patterning and specification in the developing cerebellum. Annu Rev Neurosci 1995;18:385–408.
- Komuro H, Rakic P: Orchestration of neuronal migration by activity of ion channels, neurotransmitter receptors, and intracellular Ca2+ fluctuations. J Neurobiol 1998;37:110–130.
- Parnavelas JG, Alifragis P, Nadarajah B: The origin and migration of cortical neurons. Prog Brain Res 2002;136:73–80.
- Nadarajah B, Alifragis P, Wong RO, Parnavelas JG: Neuronal migration in the developing cerebral cortex: observations based on real-time imaging. Cereb Cortex 2003;13:607–611.
- Marin O, Rubenstein JL: Cell migration in the forebrain. Annu Rev Neurosci 2003;26:441–483.
- Marin O, Rubenstein JL: A long, remarkable journey: tangential migration in the telencephalon. Nat Rev Neurosci 2001;2:780–790.
- Metin C, Baudoin JP, Rakic S, Parnavelas JG: Cell and molecular mechanisms involved in the migration of cortical interneurons. Eur J Neurosci 2006;23:894–900.
- Flint AC, Kriegstein AR: Mechanisms underlying neuronal migration disorders and epilepsy. Curr Opin Neurol 1997;10:92–97.
- Walsh CA: Genetics of neuronal migration in the cerebral cortex. MRDD Res Rev 2000;6:34–40.
- Gleeson JG: Neuronal migration disorders. MRDD Res Rev 2001;7:167–171.
- Rakic P, Cameron RS, Komuro H: Recognition, adhesion, transmembrane signaling and cell motility in guided neuronal migration. Curr Opin Neurobiol 1994;4:63–69.
- Rakic P, Komuro H: The role of receptor/channel activity in neuronal cell migration. J Neurobiol 1995;26:299–315.
- Hatten ME: Central nervous system neuronal migration. Annu Rev Neurosci 1999;22:511–539.
- Yacubova E, Komuro H: Cellular and molecular mechanisms of cerebellar granule cell migration. Cell Biochem Biophys 2003;37:213–234.
- Komuro H, Yacubova E: Recent advances in cerebellar granule cell migration. CMLS 2003;60:1084–1098.
- Hatten ME, Mason CA: Mechanisms of glial-guided neuronal migration in vitro and in vivo. Experientia 1990;46:907–916.
- Komuro H, Kumada T: Ca2+ transients control CNS neuronal migration. Cell Calcium 2005;37:387–393.
- Rakic P: Neuron-glia relationship during granule cell migration in developing cerebellar cortex: a golgi and electron microscopic study in Macacus rhesus. J Comp Neurol 1971;141:283–312.
- Rakic P: Mode of cell migration to the superficial layers of fetal monkey neocortex. J Comp Neurol 1972;145:61–83.
Grumet M, Hoffman S, Chuong CM, Edelman GM: Polypeptide components and binding functions of neuron-glia cell adhesion molecules. Proc Natl Acad Sci USA 1984;181:7989–7993.
- Hoffman S, Friedlander DR, Chuong CM, Grumet M, Edelman GM: Differential contribution of Ng-CAM and N-CAM to cell adhesion in different neural regions. J Cell Biol 1986;103:145–158.
- Chuong CM, Crossin KL, Edelman GM: Sequential expression and differential function of multiple adhesion molecules during the formation of cerebellar cortical layers. J Cell Biol 1987;104:331–342.
- Edmondson JC, Liem RKH, Kuster JE, Hatten ME: Astrotactin: a novel neuronal cell surface antigen that mediates neuron-astroglial interactions in cerebellar microcultures. J Cell Biol 1988;106:505–517.
- Komuro H, Rakic P: Modulation of neuronal migration by NMDA receptors. Science 1993;260:95–97.
- Behar TN, Schaffner AE, Scott CA, O’Connell C, Barker JL: Differential response of cortical plate and ventricular zone cells to GABA as a migration stimulus. J Neurosci 1998;18:6378–6387.
- Behar TN, Scott CA, Greene CL, Wen X, Smith SV, Maric D, Liu QY, Colton CA, Barker JL: Glutamate acting at NMDA receptors stimulates embryonic cortical neuronal migration. J Neurosci 1999;19:4449–4461.
- Hirai K, Yoshida H, Kihara M, Hasegawa K, Sakamoto T, Sawada T, Fushiki S: Inhibiting neuronal migration by blocking NMDA receptors in the embryonic rat cerebral cortex: a tissue culture study. Brain Res Dev Brain Res 1999;114:63–67.
- Komuro H, Rakic P: Dynamics of granule cell migration: a confocal microscopic study in acute cerebellar slice preparations. J Neurosci 1995;15:1110–1120.
- Komuro H, Rakic P: Distinct modes of neuronal migration in different domains of developing cerebellar cortex. J Neurosci 1998;18:1478–1490.
- Komuro H, Yacubova E, Yacubova E, Rakic P: Mode and tempo of tangential cell migration in the cerebellar external granular layer. J Neurosci 2001;21:527–540.
- Kumada T, Lakshmana ML, Komuro H: Reversal of neuronal migration in a mouse model of fetal alcohol syndrome by controlling second-messenger signalings. J Neurosci 2006;26:742–756.
- Fujita S: Quantitative analysis of cell proliferation and differentiation in the cortex of the postnatal mouse cerebellum. J Cell Biol 1967;32:277–287.
- Uzman L: The development of neonatal mouse cerebellum studied by tritiated thymidine uptake. J Comp Neurol 1960;114:137–159.
- Miale IL, Sidman RL: An autoradiographic analysis of histogenesis in the mouse cerebellum. Exp Neurol 1961;4:277–296.
- Fujita S, Shimada M, Nakamura T: H3-thymidine autoradiographic studies on the cell proliferation and differentiation in the external and the internal granular layers of the mouse cerebellum. J Comp Neurol 1966;128:191–208.
- Ryder EF, Cepko CL: Migration patterns of clonally related granule cells and their progenitors in the developing chick cerebellum. Neuron 1994;12:1011–1028.
- Yacubova E, Komuro H: Intrinsic program for migration of cerebellar granule cells in vitro. J Neurosci2002;22:5966–5981.
- Komuro H, Rakic P: Selective role of N-type calcium channels in neuronal migration. Science 1992;257:806–809.
- Komuro H, Rakic P: Intracellular Ca2+ fluctuations modulate the rate of neuronal migration. Neuron 1996;17:275–285.
- Kumada T, Komuro H: Completion of neuronal migration regulated by loss of Ca2+ transients. Proc Natl Acad Sci USA 2004;101:8479–8484.
- Rossi D, Slater TN: The developmental onset of NMDA receptor channel activity during neuronal migration. Neuropharmacology 1993;32:1239–1248.
- Farrant M, Feldmeyer D, Takahashi T, Cull-Candy SG: NMDA-receptor channel diversity in the developing cerebellum. Nature 1994;368:335–339.
- Monyer H, Burnashev N, Lauria DJ, Sakman B, Seeburg PH: Development of regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 1994;12:529–540.
- Rocamora N, Garcia LF, Palacios JM, Mengod G: Differential expression of brain-derived neurotrophic factor, neurotrophin-3, and low-affinity nerve growth factor receptor during the postnatal development of the rat cerebellar system. Brain Res Mol Brain Res 1993;17:1–8.
- Segal R, Pomeroy S, Stiles C: Axonal growth and fasciculation linked to differential expression of BDNF and NT3 receptors in developing cerebellar granule cells. J Neurosci 1995;15:4970–4981.
- Borghesani PR, Peyrin JM, Klein R, Rubin J, Carter AR, Schwartz PM, Luster A, Corfas G, Segal RA: BDNF stimulates migration of cerebellar granule cells. Development 2002;129:1435–1442.
- Ernfors P, Merlio JP, Persson H: Cells expressing mRNA for neurotrophins and their receptors during embryonic rat development. Eur J Neurosci 1992;4:1140–1158.
- Neveu I, Arenas B: Neurotrophins promote the survival and development of neurons in the cerebellum of hypothyroid rats in vivo. J Cell Biol 1996;133:631–646.
- Lindholm D, Castren E, Tsoulfas P, Kolbeck R, Berzaghi MDP, Leingartner A, Heisenberg CP, Tessarollo L, Parada LF, Thoenen H: Neurotrophin-3 induced tri-iodothyronine in cerebellar granule cells promotes Purkinje cell differentiation. J Cell Biol 1993;122:443–450.
- Doughty ML, Lohof A, Campana A, Delhaye-Bouchaud N, Mariani J: Neurotrophin-3 promotes cerebellar granule cell exit from the EGL. Eur J Neurosci 1998;10:3007–3011.
- Rio C, Rieff HI, Qi P, Khurana TS, Corfas G: Neuregulin and erbB receptors play a critical role in neuronal migration. Neuron 1997;19:39–50.
- Zou YR, Kottmann AH, Kuroda M, Taniuchi I, Littman DR: Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 1998;393:595–599.
- McGrath K, Koniski AD, Maltby KM, McGann JK, Palis J: Embryonic expression and function of the chemokine SDF-1 and its receptor, CXCR4. Dev Biol 1999;213:442–456.
- Ma Q, Jones D, Borghesani PR, Segal RA, Nagasawa T, Kishimoto T, Bronson RT, Springer TA: Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc Natl Acad Sci USA 1998;95:9448–9453.
- Klein RS, Rubin JB, Gibson HD, DeHaan EN, Alvarez-Hernandez X, Segal RA, Luster AD: SDF-1α induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells. Development 2001;128:1971–1981.
- Lu Q, Sun EE, Klein RS, Flanagan JG: Ephrin-B reverse signaling is mediated by a novel PDZ-RGS protein and selectively inhibits G protein-coupled chemoattraction. Cell 2001;105:69–79.
- Adams NC, Tomoda T, Cooper M, Dietz G, Hatten ME: Mice that lack astrotactin have slowed neuronal migration. Development 2002;129:965–972.
- Husmann K, Faissner A, Schachner M: Tenascin promotes cerebellar granule cell migration and neurite outgrowth by different domains in the fibronectin type III repeats. J Cell Biol 1992;116:1475–1486.
- Friedman GC, Seeds NW: Tissue plasminogen activator mRNA expression in granule neurons coincides with their migration in the developing cerebellum. J Comp Neurol 1995;360:658–670.
- Verrall S, Seeds NW: Characterization of 125I-tissue plasminogen activator binding to cerebellar granule neurons. J Cell Biol 1989;109:265–271.
- Seeds NW, Basham ME, Haffke SP: Neuronal migration is retarded in mice lacking the tissue plasminogen activator gene. Proc Natl Acad Sci USA 1999;96:14118–14123.
- Stewart RM, Richman DP, Caviness VSJ: Lissencephaly and pachygyria: an architectonic and topographic analysis. Acta Neuropathol 1975;31:1–12.
Jellinger K, Rett A: Agyria-pachygyria (lissencephaly syndrome). Neuropediatrics 1976;7:6691.
- Miller J: Lissencephaly in two siblings. Neurology 1963;13:841–850.
- Reiner O, Albrecht U, Gordon M, Chianese KA, Wong C, Gal-Gerber O, Sapir T, Siracusa LD, Buchberg AM, Caskey CT: Lissencephaly gene (LIS1) expression in the CNS suggests a role in neuronal migration. J Neurosci 1995;15:3730–3738.
- Hattori M, Arai H, Inoue K: Purification and characterization of bovine brain platelet-activating factor acetylhydrolase. J Biol Chem 1993;268:18748–18753.
- Hattori M, Hideki A, Tsujimoto M, Arai H, Inoue K: Catalytic subunit of bovine brain platelet-activating factor acetylhydrolase is a novel type of serine esterase. J Biol Chem 1994;269:23150–23155.
- Clark GD, McNeil RS, Bix GJ, Swann JW: Platelet-activating factor produces neuronal growth cone collapse. Neuroreport 1995;6:2569–2575.
- Bix GJ, Clark GD: Platelet-activating factor receptor stimulation disrupts neuronal migration in vitro. J Neurosci 1998;18:307–318.
- Sherr CJ: Mammalian G1 cyclins. Cell 1993;73:1059–1065.
- Tsai L-H, Takahashi T, Caviness VSJ, Harlow E: Activity and expression pattern of cyclin-dependent kinase-5 in the embryonic mouse central nervous system. Development 1993;119:1029–1040.
- Ohshima T, Gilmore EC, Longenecker G, Jacobowitz DM, Brady RO, Herrup K, Kulkarni AB: Migration defects of cdk5–/– neurons in the developing cerebellum is cell autonomous. J Neurosci 1999;19:6017–6026.
- Santiago MF, Berredo-Pinho M, Costa MR, Gandra M, Cavalcante LA, Mendez-Otero R: Expression and function of ganglioside 9-O-acetyl GD3 in postmitotic granule cell development. Mol Cell Neurosci 2001;17:488–499.
- Schindler M, Humphrey PPA, Emson PC: Somatostatin receptors in the central nervous system. Prog Neurobiol 1996;50:9–47.
- Patel YC: Molecular pharmacology of somatostatin receptor subtypes. J Endocrinol Invest 1997;20:348–367.
- Viollet C, Bodenant C, Prunotto C, Roosterman D, Schaefer J, Meyerhof W, Epelbaum J, Vaudry H, Leroux P: Differential expression of multiple somatostatin receptors in rat cerebellum during development. J Neurochem1997;68:2263–2272.
- Naus CCG: Developmental appearance of somatostatin in the rat cerebellum: in situ hybridization and immunohistochemistry. Brain Res Bul 1990;24:583–592.
- Yacubova E, Komuro H: Stage-specific control of neuronal migration by somatostatin. Nature 2002;415:77–81.
- Deo DD, Bazan NG, Hunt JD: Activation of platelet-activating factor receptor-coupled Gαq leads to stimulation of Src and focal adhesion kinase via two separate pathways in human umbilical vein endothelial cells. J Biol Chem 2004;279:3497–3508.
- Princen K, Hatse S, Vermeire K, De Clercq E, Schols D: Evaluation of SDF-1/CXCR4-induced Ca2+ signaling by fluorometric imaging plate reader (FLIP) and flow cytometry. Cytometry 2003;51:35–45.
- Roland J, Murphy BJ, Ahr B, Robert-Hebmann V, Delauzun V, Nye KE: Role of the intracellular domains of CXCR4 in SDF-1-mediated signaling. Blood 2003;101:399–406.
- Fernandez-Monreal M, Lopez-Atalaya JP, Benchenane K, Leveille F, Cacquevel M, Plawinski L, MacKenzie ET, Bu G, Buisson A, Vivien D: Is tissue-type plasminogen activator a neuromodulator? Mol Cell Neurosci 2004;25:594–601.
- Pantazis NJ, West JR, Dai D: The nitric oxide-cyclic GMP pathway plays an essential role in both promoting cell survival of cerebellar granule cells in culture and protecting the cells against ethanol neurotoxicity. J Neurochem 1998;70:1826–1838.
- Tentler JJ, Hadcock JR, Gutierrez-Hartmann A: Somatostatin acts by inhibiting the cyclic 3′,5′-adenosine monophosphate (cAMP)/protein kinase A pathway, cAMP response element-binding protein (CREB) phosphorylation, and CREB transcription potency. Mol Endocrinol 1997;11:859–866.
- Gunn-Moore F, Williams AG, Tavare JM: Analysis of mitogen-activated protein kinase activation by naturally occurring splice variants of TrkC, the receptor for neurotrophin-3. Biochem J 1997;322:193–198.
- Yuen EC, Mobley WC: Early BDNF, NT-3, and NT-4 signaling events. Exp Neurol 1999;159:297–308.
- Du Y, Lercher LD, Zhou R, Dreyfus CF: Mitogen-activated protein kinase pathway meditates effects of brain-derived neurotrophic factor on differentiation of basal forebrain oligodendrocytes. J Neurosci Res 2006;84:1692–1702.
- Pareek TK, Kulkarni AB: Cdk5: a new player in pain signaling. Cell Cycle 2006;5:585–588.
- Clarren SK, Smith DW: The fetal alcohol syndrome. N Engl J Med 1978;298:1063–1067.
- Clarren SK, Alvord EC, Sumi SM: Brain malformations related to prenatal exposure to ethanol. J Pediatr 1978;92:64–67.
- Marcus JC: Neurological findings in the fetal alcohol syndrome. Neuropediatrics 1987:18:158–160.
- Jones KL, Smith DW: Recognition of the fetal alcohol syndrome in early infancy. Lancet 1973;2:999–1001.
- Committee on Substace Abuse: Fetal alcohol syndrome and fetal alcohol effects. Pediatrics 1993;91:1004–1006.
- Clarren SK, Astley SJ, Bowden DM, Lai H, Milam AH, Rudeen PK, Shoemaker WJ: Neuroanatomic and neurochemical abnormalities in nonhuman primate infants exposed to weekly dose of ethanol during gestation. Alcohol Clin Exp Res 1990;14:674–683.
- Wisniewski K, Damabska M, Sher JH, Qazi Q: A clinical neuropathological study of the fetal alcohol syndrome. Neuropediatrics 1983;14:197–205.
- Coffin JM, Baroody S, Schneider K, O’Neill J: Impaired cerebellar learning in children with prenatal alcohol exposure: a comparative study of eyeblink conditioning in children with ADHD and dyslexia. Cortex 2005;41:389–398.
- Manzardo AM, Penick EC, Knop J, Nickel EJ, Hall S, Jensen P, Gabrielli WF Jr: Developmental differences in childhood motor coordination predict adult alcohol dependence: proposed role for the cerebellum in alcoholism. Alcohol Clin Exp Res 2005;29:353–357.
- Costa LG, Vitalone A, Guizzetti M: Signal transduction mechanisms involved in the antiproliferative effects of ethanol in glial cells. Toxicol Lett 2004;149:67–73.
- Olney JW: Fetal alcohol syndrome at the cellular level. Addict Biol 2004;9:137–149.
- West JR, Chen WJ, Pantazis NJ: Fetal alcohol syndrome: the vulnerability of the developing brain and possible mechanisms of damage. Metab Brain Dis 1994;9:291–322.
- Kennedy LA: The pathogenesis of brain abnormalities in the fetal alcohol syndrome: an integrating hypothesis. Teratology 1984;29:363–368.
- Guerri C: Mechanisms involved in central nervous system dysfunctions induced by prenatal ethanol exposure. Neurotox Res 2002;4:327–335.
- Miller MW: Effects of alcohol on the generation and migration of cerebral cortical neurons. Science 1986;233:1308–1311.
- Miller MW: Migration of cortical neurons is altered by gestational exposure to ethanol. Alcohol Clin Exp Res 1993;17:304–314.
- Peiffer J, Majewski F, Fischbach H, Bierich JR, Volk B: Alcohol embryo and fetopathy. J Neurol Sci 1979;41:125–137.
- Coulter CL, Leech RW, Schaefer GB, Scheithauer BW, Brumback RA: Midline cerebral dysgenesis, dysfunction of the hypothalamic-pituitary axis, and fetal alcohol effects. Arch Neurol 1993;50:771–775.
- Dikranian K, Qin YQ, Labruyere J, Nemmers B, Olney JW: Ethanol-induced neuroapoptosis in the developing rodent cerebellum and related brain stem structures. Dev Brain Res 2005;155:1–13.
- Sakata-Haga H, Sawada K, Hisano S, Fukui Y: Abnormalities of cerebellar foliation in rats prenatally exposed to ethanol. Acta Neuropathol 2001;102:36–40.
- Kornguth SE, Rutledge JJ, Sunderland E, Siegel F, Carlson I, Smollens J, Juhl U, Young B: Impeded cerebellar development and reduced serum thyroxine levels associated with fetal alcohol intoxication. Brain Res 1979;177:347–360.
- Bauer-Moffet C, Altman J: Ethanol-induced reductions in cerebellar growth of infant rats. Expl Neurol 1975;48:378–382.
- Borges S, Lewis PD: Effects of ethanol on postnatal cell acquisition in the rat cerebellum. Brain Res 1983;271:388–391.
- Kotkoskie LA, Norton S: Prenatal brain malformations following acute ethanol exposure in the rat. Alcohol Clin Exp Res 1988;12:831–836.
- Siegenthaler JA, Miller MW: Transforming growth factor β1 modulates cell migration in rat cortex: effects of ethanol. Cerebral Cortex 2004;14:791–802.
- Panicker AK, Buhusi M, Thelen K, Maness PF: Cellular signaling mechanisms of neural cell adhesion molecules. Front Biosci 2003;8:d900–d911.
- Charness ME, Safran RM, Perides G: Ethanol inhibits neural cell-cell adhesion. J Biol Chem 1994;269:9304–9309.
- Miller MW, Luo J: Effects of ethanol and transforming growth factor β (TGFβ) on neuronal proliferation and nCAM expression. Alcohol Clin Exp Res 2002;26:1281–1285.
- Bauer-Moffet C, Altman J: The effect of ethanol chronically administrated to preweanling rats on cerebellar development: a morphological study. Brain Res 1977;119:249–268.
- Jones DG: Influence of ethanol on neuronal and synaptic maturation in the central nervous system – morphological investigations. Prog Neurobiol 1988;31:171–197.
- West JR, Chen WJ, Pantazis NJ: Fetal alcohol syndrome: the vulnerability of the developing brain and possible mechanisms of damage. Metab Brain Dis 1994;9:291–322.
- Shetty AK, Phillips DE: Effects of prenatal ethanol exposure on the development of Bergmann glia and astrocytes in the rat cerebellum: an immunohistochemical study. J Comp Neurol 1992;321:19–32.
- Peoples RW, Li C, Weight FF: Lipid versus protein theories of alcohol action in the nervous system. Annu Rev Pharmacol Toxicol 1996;36:185–201.
- Walter HJ, Messing RO: Regulation of neuronal voltage-gated calcium channels by ethanol. Neurochem Int 1999;35:95–101.
- Lovinger DM, White G, Weight FF: Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science 1989;243:1721–1724.
- Mezna M, Patchick T, Tovey S, Michelangeli F: Inhibition of the cerebellar inositol 1,4,5-trisphosphate-sensitive Ca2+ channel by ethanol and other aliphatic alcohols. Biochem J 1996;314:175–179.
- Yang S, Huang XY: Ca2+ influx through L-type Ca2+ channels controls the trailing tail contraction in growth factor-induced fibroblast cell migration. J Biol Chem 2005;280:27130–27137.
- Titus B, Schwartz MA, Theodorescu D: Rho proteins in cell migration and metastasis. Crit Rev Eukaryot Gene Expr 2005;15:103–114.
- Rajalingam K, Wunder C, Brinkmann V, Churin Y, Hekman M, Sievers C, Rapp UR, Rudel T: Prohibition is required for Ras-induced Raf-MEK-ERK activation and epithelial cell migration. Nat Cell Biol 2005;7:837–843.
- Tabakoff B, Nelson E, Yoshimura M, Hellevuo K, Hoffman PL: Phosphorylation cascades control the actions of ethanol on cell cAMP signaling. J Biomed Sci 2001;8:44–51.
- Maeno-Hikichi Y, Chang S, Matsumura K, Lai M, Lin H, Nakagawa N, Kuroda S, Zhang JF: A PKC epsilon-ENH-channel complex specifically modulates N-type Ca2+ channels. Nat Neurosci 2003;6:468–475.
- Zsombok A, Schrofner S, Hermann A, Kerschbaum HH: A cGMP-dependent cascade enhances an L-type-like Ca2+ current in identified snail neurons. Brain Res 2005;1032:70–76.
- Straub SV, Wagner LE 2nd, Bruce JI, Yule DI: Modulation of cytosolic calcium signaling by protein kinase A-mediated phosphorylation of inositol 1,4,5-triphosphate receptors. Biol Res 2004;37:593–602.
- Tasken K, Aandahl EM: Localized effects of cAMP mediated by distinct routes of protein kinase A. Physiol Rev 2004;84:137–167.
- Gomez LL, Alam S, Smith KE, Horne E, Dell’Acqua ML: Regulation of A-kinase anchoring protein 79/150 cAMP-dependent protein kinase postsynaptic targeting by NMDA receptor activation of calcineurin and remodeling of dendritic actin. J Neurosci 2002;22:7027–7044.
- Price LS, Langeslag M, ten Klooster JP, Hordijk PL, Jalink K, Collard, JG: Calcium signaling regulates translocation and activation of Rac. J Biol Chem 2003;278:39413–39421.
- Howe AK: Regulation of actin-based cell migration by cAMP/PKA. Biochem Biophys Acta 2004;1692:159–174.
- Tsuji R, Guizzetti M, Costa LG: In vivo ethanol decreases phosphorylated MAPK and p70S6 kinase in the developing rat brain. Neuroreport 2003;14:1395–1399.
- Tang N, He M, O’Riordan MA, Farkas C, Buck K, Lemmon V, Bearer CF: Ethanol inhibits L1 cell adhesion molecule activation of mitogen-activated protein kinases. J Neurochem 2006;96:1480–1490.
- Segal RA, Greenberg ME: Intracellular signaling pathway activated by neurotrophic factors. Annu Rev Neurosci 1996:19:463–489.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.