The Korean Journal of Physiology and Pharmacology

  • 제24권1호
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  • Pages.121-126
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  • 2020
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  • 1226-4512(pISSN)
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  • 2093-3827(eISSN)
대한약리학회 (The Korean Society of Pharmacology)
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Ezrin-radixin-moesin proteins are regulated by Akt-GSK3β signaling in the rat nucleus accumbens core

  • Kim, Wha Young (Department of Physiology, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine) ;
  • Cai, Wen Ting (Department of Medical Science, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine) ;
  • Jang, Ju Kyong (Bio-Pharm Solutions Co., Ltd.) ;
  • Kim, Jeong-Hoon (Department of Physiology, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine)
  • 투고 : 2019.11.05
  • 심사 : 2019.11.20
  • 발행 : 2020.01.01
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초록

The ezrin-radixin-moesin (ERM) proteins are a family of membrane-associated proteins known to play roles in cell-shape determination as well as in signaling pathways. We have previously shown that amphetamine decreases phosphorylation levels of these proteins in the nucleus accumbens (NAcc), an important neuronal substrate mediating rewarding effects of drugs of abuse. In the present study, we further examined what molecular pathways may be involved in this process. By direct microinjection of LY294002, a PI3 kinase inhibitor, or of S9 peptide, a proposed GSK3β activator, into the NAcc core, we found that phosphorylation levels of ERM as well as of GSK3β in this site are simultaneously decreased. These results indicate that ERM proteins are under the regulation of Akt-GSK3β signaling pathway in the NAcc core. The present findings have a significant implication to a novel signal pathway possibly leading to structural plasticity in relation with drug addiction.

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참고문헌

  1. Bretscher A, Edwards K, Fehon RG. ERM proteins and merlin: integrators at the cell cortex. Nat Rev Mol Cell Biol. 2002;3:586-599. https://doi.org/10.1038/nrm882
  2. Louvet-Vallee S. ERM proteins: from cellular architecture to cell signaling. Biol Cell. 2000;92:305-316. https://doi.org/10.1016/S0248-4900(00)01078-9
  3. Niggli V, Rossy J. Ezrin/radixin/moesin: versatile controllers of signaling molecules and of the cortical cytoskeleton. Int J Biochem Cell Biol. 2008;40:344-349. https://doi.org/10.1016/j.biocel.2007.02.012
  4. Pelaseyed T, Bretscher A. Regulation of actin-based apical structures on epithelial cells. J Cell Sci. 2018;131:jcs221853. https://doi.org/10.1242/jcs.221853
  5. Matus A. Growth of dendritic spines: a continuing story. Curr Opin Neurobiol. 2005;15:67-72. https://doi.org/10.1016/j.conb.2005.01.015
  6. Neisch AL, Fehon RG. Ezrin, Radixin and Moesin: key regulators of membrane-cortex interactions and signaling. Curr Opin Cell Biol. 2011;23:377-382. https://doi.org/10.1016/j.ceb.2011.04.011
  7. Robbins TW, Cador M, Taylor JR, Everitt BJ. Limbic-striatal interactions in reward-related processes. Neurosci Biobehav Rev. 1989; 13:155-162. https://doi.org/10.1016/S0149-7634(89)80025-9
  8. Koob GF, Le Moal M. Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology. 2001;24:97-129. https://doi.org/10.1016/S0893-133X(00)00195-0
  9. Goto Y, Grace AA. Limbic and cortical information processing in the nucleus accumbens. Trends Neurosci. 2008;31:552-558. https://doi.org/10.1016/j.tins.2008.08.002
  10. Nestler EJ. Is there a common molecular pathway for addiction? Nat Neurosci . 2005;8:1445-1449. https://doi.org/10.1038/nn1578
  11. Kim WY, Shin SR, Kim S, Jeon S, Kim JH. Cocaine regulates ezrinradixin-moesin proteins and RhoA signaling in the nucleus accumbens. Neuroscience. 2009;163:501-505. https://doi.org/10.1016/j.neuroscience.2009.06.067
  12. Kim WY, Jang JK, Shin JK, Kim JH. Amphetamine dephosphorylates ERM proteins in the nucleus accumbens core and lithium attenuates its effects. Neurosci Lett. 2013;552:103-107. https://doi.org/10.1016/j.neulet.2013.07.037
  13. Beaulieu JM, Caron MG. Looking at lithium: molecular moods and complex behaviour. Mol Interv. 2008;8:230-241. https://doi.org/10.1124/mi.8.5.8
  14. Beaulieu JM, Del'guidice T, Sotnikova TD, Lemasson M, Gainetdinov RR. Beyond cAMP: The regulation of Akt and GSK3 by dopamine receptors. Front Mol Neurosci. 2011;4:38. https://doi.org/10.3389/fnmol.2011.00038
  15. Li B, Ren J, Yang L, Li X, Sun G, Xia M. Lithium inhibits GSK3${\beta}$ activity via two different signaling pathways in neurons after spinal cord injury. Neurochem Res. 2018;43:848-856. https://doi.org/10.1007/s11064-018-2488-9
  16. Gallo G. Semaphorin 3A inhibits ERM protein phosphorylation in growth cone filopodia through inactivation of PI3K. Dev Neurobiol. 2008;68:926-933. https://doi.org/10.1002/dneu.20631
  17. Jeon S, Park JK, Bae CD, Park J. NGF-induced moesin phosphorylation is mediated by the PI3K, Rac1 and Akt and required for neurite formation in PC12 cells. Neurochem Int. 2010;56:810-818. https://doi.org/10.1016/j.neuint.2010.03.005
  18. Cencetti F, Bernacchioni C, Bruno M, Squecco R, Idrizaj E, Berbeglia M, Bruni P, Donati C. Sphingosine 1-phosphate-mediated activation of ezrin-radixin-moesin proteins contributes to cytoskeletal remodeling and changes of membrane properties in epithelial otic vesicle progenitors. Biochim Biophys Acta Mol Cell Res. 2019;1866:554-565. https://doi.org/10.1016/j.bbamcr.2018.12.007
  19. Choi JM, Ahn MH, Chae WJ, Jung YG, Park JC, Song HM, Kim YE, Shin JA, Park CS, Park JW, Park TK, Lee JH, Seo BF, Kim KD, Kim ES, Lee DH, Lee SK, Lee SK. Intranasal delivery of the cytoplasmic domain of CTLA-4 using a novel protein transduction domain prevents allergic inflammation. Nat Med. 2006;12:574-579. https://doi.org/10.1038/nm1385
  20. Dajani R, Fraser E, Roe SM, Young N, Good V, Dale TC, Pearl LH. Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition. Cell. 2001;105:721-732. https://doi.org/10.1016/S0092-8674(01)00374-9
  21. Frame S, Cohen P, Biondi RM. A common phosphate binding site explains the unique substrate specificity of GSK3 and its inactivation by phosphorylation. Mol Cell. 2001;7:1321-1327. https://doi.org/10.1016/S1097-2765(01)00253-2
  22. Pellegrino LJ, Pellegrino AS, Cushman AJ. A stereotaxic atlas of the rat brain. New York: Plenum; 1979.
  23. Kim WY, Jang JK, Lee JW, Jang H, Kim JH. Decrease of GSK3${\beta}$ phosphorylation in the rat nucleus accumbens core enhances cocaine-induced hyper-locomotor activity. J Neurochem. 2013;125: 642-648. https://doi.org/10.1111/jnc.12222
  24. O'Donnell KC, Gould TD. The behavioral actions of lithium in rodent models: leads to develop novel therapeutics. Neurosci Biobehav Rev. 2007;31:932-962. https://doi.org/10.1016/j.neubiorev.2007.04.002
  25. Jin EJ, Ko HR, Hwang I, Kim BS, Choi JY, Park KW, Cho SW, Ahn JY. Akt regulates neurite growth by phosphorylation-dependent inhibition of radixin proteasomal degradation. Sci Rep. 2018;8:2557. https://doi.org/10.1038/s41598-018-20755-w
  26. Jeong HJ, Kim JH, Jeon S. Amphetamine-induced ERM proteins phosphorylation is through PKC${\beta}$ activation in PC12 cells. Korean J Physiol Pharmacol. 2011;15:245-249. https://doi.org/10.4196/kjpp.2011.15.4.245
  27. Shen HW, Toda S, Moussawi K, Bouknight A, Zahm DS, Kalivas PW. Altered dendritic spine plasticity in cocaine-withdrawn rats. J Neurosci. 2009;29:2876-2884. https://doi.org/10.1523/JNEUROSCI.5638-08.2009
  28. Abraham WC. Metaplasticity: tuning synapses and networks for plasticity. Nat Rev Neurosci. 2008;9:387-399. https://doi.org/10.1038/nrn2356
  29. Li Y, Acerbo MJ, Robinson TE. The induction of behavioural sensitization is associated with cocaine-induced structural plasticity in the core (but not shell) of the nucleus accumbens. Eur J Neurosci. 2004;20:1647-1654. https://doi.org/10.1111/j.1460-9568.2004.03612.x
  30. Robinson TE, Kolb B. Structural plasticity associated with exposure to drugs of abuse. Neuropharmacology. 2004;47 Suppl 1:33-46. https://doi.org/10.1016/j.neuropharm.2004.06.025
  31. Lee KW, Kim Y, Kim AM, Helmin K, Nairn AC, Greengard P. Cocaine-induced dendritic spine formation in D1 and D2 dopamine receptor-containing medium spiny neurons in nucleus accumbens. Proc Natl Acad Sci U S A . 2006;103:3399-3404. https://doi.org/10.1073/pnas.0511244103
  32. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 5th ed. London: Elsevier Academic; 2004.