$\require{mediawiki-texvc}$
  • 검색어에 아래의 연산자를 사용하시면 더 정확한 검색결과를 얻을 수 있습니다.
  • 검색연산자
검색연산자 기능 검색시 예
() 우선순위가 가장 높은 연산자 예1) (나노 (기계 | machine))
공백 두 개의 검색어(식)을 모두 포함하고 있는 문서 검색 예1) (나노 기계)
예2) 나노 장영실
| 두 개의 검색어(식) 중 하나 이상 포함하고 있는 문서 검색 예1) (줄기세포 | 면역)
예2) 줄기세포 | 장영실
! NOT 이후에 있는 검색어가 포함된 문서는 제외 예1) (황금 !백금)
예2) !image
* 검색어의 *란에 0개 이상의 임의의 문자가 포함된 문서 검색 예) semi*
"" 따옴표 내의 구문과 완전히 일치하는 문서만 검색 예) "Transform and Quantization"
쳇봇 이모티콘
안녕하세요!
ScienceON 챗봇입니다.
궁금한 것은 저에게 물어봐주세요.

논문 상세정보

초록

신경전달물질의 분비는 시냅스전 신경말단의 active zone에 있는 다양한 단백질들에 의해 조절된다. 도파민은 정신분열병, 약물중독과 같은 여러 가지 행동, 정신질환의 병태생리와 연관된 필수적인 신경전달물질이다. 저자들은 본 연구에서 신경 전달물질 분비와 관련된 주요 유전자가 결여 된 knockout (KO) 생쥐의 시냅토좀(synaptosome) 도파민 분비를 측정하였다. 시냅토좀 도파민 흡수와 분비는 [$^3H$]-도파민과 관류실험을 이용하여 시행, 측정하였다. 17 KO 생쥐 가운데 3 종류의 생쥐에서 그들의 littermate 대조군과 비교하였을 때 변화된 도파민 분비를 보였다. $Rim1{\alpha}$ KO에서 세포막 탈분극에 의한 [$^3H$]-도파민은 유의하게 감소되었으며, 또한 $Rim1{\alpha}$의 도파민 신경에서의 조건 KO에서는 생리적 완충용액에 의한 기본적인 도파민 분비 및 세포막 탈분극에 의한 도파민 분비 모두가 유의하게 감소되어 있었다. neurexin3의 도파민 신경에서의 조건 KO에서는 세포막 탈분극에 의한 도파민 분비의 증가를 보였다. 이 데이터들은 도파민 분비와 글루타메이트, GABA와 같은 전통적 신경전달물질 분비의 유사성과 차별성을 설명한다. 결론적으로, $Rim1{\alpha}$와 neurexin3는 시냅스전 도파민 분비의 중요한 조절자이며 신경계 질환과 연관될 가능성이 있다.

Abstract

Neurotransmitter release is regulated by various proteins of the active zone in the presynaptic nerve terminals. Dopamine (DA) is an essential neurotransmitter associated with the pathophysiology of diverse behavioral and mental illness such as schizophrenia and drug addiction. We measured synaptosomal DA release of knockout (KO) mice which lacked major genes related to neurotransmitter release. Synaptosomal DA uptake and release were performed and measured using [$^3H$]-DA and superfusion experiments. 3 of the 17 KO mice exhibited altered DA release compared to their littermate controls. In $Rim1{\alpha}$ KO, [$^3H$]-DA release evoked by membrane depolarization significantly decreased. Both basal (physiological buffer-evoked) and membrane depolarization-evoked DA release significantly decreased in dopaminergic conditional KO of $Rim1{\alpha}{\beta}$. Dopaminergic conditional KO of neurexin3 demonstrated a significant increase of membrane depolarization-evoked DA release. These data explain the similarities and distinctions between DA and other classical neurotransmitters such as glutamate and GABA ($\gamma$-aminobutyric acid) release. In conclusion, $Rim1{\alpha}$ and neurexin3 may be important regulators of presynaptic DA release and related to disorders of the nervous system.

참고문헌 (33)

  1. Alloisio, S., C. Cervetto, M. Passalacqua, R. Barbieri, G. Maura, M. Nobile, and M. Marcoli. 2008. Functional evidence for presynaptic P2X7 receptors in adult rat cerebrocortical nerve terminals. FEBS Lett. 582, 3948-3953 
  2. Arac, D., A A Boucard, E. Ozkan, P. Strop, E. Newell, T. C. Sudhof, and A T. Brunger. 2007. Structures of neuroligin- 1 and the neuroligin-1/neurexin-1 beta complex reveal specific protein-protein and protein-Ca2+ interactions. Neuron 56, 992-1003 
  3. Boucard, A A, A A Chubykin, D. Comoletti, P. Taylor, and T. C. Sudhof. 2005. A splice code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to alpha- and beta-neurexins. Neuron 48, 229-236 
  4. Chandra, S., F. Fornai, H. B. Kwon, U. Yazdani, D. Atasoy, X. Liu, R. E. Hammer, G. Battaglia, D. C. German, P. E. Castillo, and T. C. Sudhof. 2004. Double-knockout mice for alpha- and beta-synucleins: effect on synaptic functions. Proc. Natl. Acad. Sci. USA 101, 14966-14971 
  5. Chandra, S., G. Gallardo, R. Fernandez-Chacon, O. M. Schluter, and T. C. Sudhof. 2005. Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell 123, 383-396 
  6. Deak F., O. H Shin, J. Tang, P. Hanson, J. Ubach, R Jahn, J. Rizo, E. T. Kavalali and T. C. Sudhof. 2006. Rabphilin regulates SNARE-dependent re-priming of synaptic vesicles for fusion. EMBO J. 25, 2856-2866 
  7. Gerber, S. H, J. Garcia, J. Rizo, and T. C. Sudhof. 2001. An unusual C(2)-domain in the active-zone protein piccolo: implications for Ca(2+) regulation of neurotransmitter release. EMBO J. 20, 1605-1619 
  8. Gerber, S. H., J. c. Rah, S. W. Min, X. Liu, H de Wit, I. Dulubova, A. C. Meyer, J. Rizo, M. Arancillo, R E. Hammer, M. Verhage, C. Rosenmund, and T. C. Sudhof. 2008. Conformational switch of syntaxin-1 controls synaptic vesicle fusion. Science 321, 1507-1510 
  9. Goto, Y, S. Otani, and A. A. Grace. 2007. The Yin and Yang of dopamine release: a new perspective. Neuropharmacology 53, 583-587 
  10. Hata, Y, B. Davletov, A. G. Petrenko, R Jahn, and T. C. Sudhof. 1993. Interaction of synaptotagmin with the cytoplasmic domains of neurexins. Neuron 10, 307-315 
  11. Heard-Costa, N. 1., M. C. Zillikens, K. 1. Monda, A. Johansson, T. B. Harris, M. Fu, T. Haritunians, M. F. Feitosa, T. Aspelund, G. Eiriksdottir, M. Garcia, 1. J. Launer, A. V. Smith, B. D. Mitchell, P. F. McArdle, A. R Shuldiner, S. J. Bielinski, E. Boerwinkle, F. Brancati, E. W. Demerath, J. S. Pankow, A. M. Arnold, Y D. Chen, N. 1. Glazer, B. McKnight, B. M. Psaty, J. I. Rotter, N. Amin, H Campbell, U. Gyllensten, C. Pattaro, P. P. Pramstaller, I. Rudan, M. Struchalin, V. Vitart, X. Gao, A. Kraja, M. A. Province, Q. Zhang, 1. D. Atwood, J. Dupuis, J. N. Hirschhorn, C. E. Jaquish, c. J. O'Donnell, R S. Vasan, C. C. White, Y S. Aulchenko, K. Estrada, A. Hofman, F. Rivadeneira, A. G. Uitterlinden, J. C. Witteman, B. A. Oostra, R C. Kaplan, V. Gudnason, J. R O'Connell, I. B. Borecki, C. M. van Duijn, 1. A. Cupples, C. S. Fox, and K. E. North. 2009. NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium. PLoS Genet. 5, e100053 
  12. Janz, R, T. C. Sudhof, R E. Hammer, V. Unni, S. A. Siegelbaum, and V. Y Bolshakov. 1999. Essential roles in synaptic plasticity for synaptogyrin I and synaptophysin I. Neuron 24, 687-700 
  13. Juranek, L K. Mukhe~ee, M. Rickmann, H Martens, J. Calka, T. C. Sudhof, and R Jahn. 2006. Differential expression of active zone proteins in neuromuscular junctions suggests functional diversification. Eur. J. Neurosci. 24, 3043-3052 
  14. Kaeser, P. S., H B. Kwon, J. Blundell, V. Chevaleyre, W. Morishita, R C. Malenka, C. M. Powell, P. E. Castillo, and T. C. Sudhof. 2008. RIMlalpha phosphorylation at serine-413 by protein kinase A is not required for presynaptic long-term plasticity or learning. Proc. Natl. Acad. Sci. USA 105, 14680-14685 
  15. Kaeser, P. S., H B. Kwon, C. Q. Chiu, 1. Deng, P. E. Castillo, and T. C. Sudhof. 2008. RIMlalpha and RIMlbeta are synthesized from distinct promoters of the RIM1 gene to mediate differential but overlapping synaptic functions. J. Neurosci. 28, 13435-13447 
  16. Khvotchev, M., G. Lonart, and T. C. Sudhof. 2000. Role of calcium in neurotransmitter release evoked by alpha-Iatrotoxin or hypertonic sucrose. Neuroscience 101, 793-802 
  17. Khvotchev, M. and T. C. Sudhof. 2000. alpha-Iatrotoxin triggers transmitter release via direct insertion into the presynaptic plasma membrane. EMBO J. 19, 3250-3262 
  18. Khvotchev, M. V. and T. C. Sudhof. 2004. Stimulus-dependent dynamic homo- and heteromultimerization of synaptobrevin/ V AMP and synaptophysin. Biochemistry 43, 15037-15043 
  19. Kremer, T., C. Kempf, N. Wittenmayer, R Nawrotzki, T. Kuner, J. Kirsch, and T. Dresbach. 2007. Mover is a novel vertebrate-specific presynaptic protein with differential distribution at subsets of CNS synapses. FEBS Lett. 581, 4727-4733 
  20. Li, H, C. L. Waites, R G. Staat Y Dobryy, J. Park, D. L. Sulzer, and R H Edwards. 2005. Sorting of vesicular monoamine transporter 2 to the regulated secretory pathway confers the somatodendritic exocytosis of monoamines. Neuron 48, 619-633 
  21. Missler, M., W. Zhang, A. Rohlmann, G. Kattenstroth, R E. Hammer, K. Gottmann, and T. C. Sudhof. 2003. Alpha-neurexins couple Ca2+ channels to synaptic vesicle exocytosis. Nature 423, 939-948 
  22. Pang, Z. P., J. Sun, J. Rizo, A. Maximov, and T. C. Sudhof. 2006. Genetic analysis of synaptotagmin 2 in spontaneous and Ca2+-triggered neurotransmitter release. EMBO J. 25, 2039-2050 
  23. Pennington, J. M., J. Millar, 1. J. CP, C. A. Owesson, D. P. McLaughlin, and J. A. Stamford. 2004. Simultaneous real- time amperometric measurement of catecholamines and serotonin at carbon fibre 'dident' microelectrodes. J. Neurosci. Methods 140, 5-13 
  24. Ridley, R M. 1994. The psychology of perserverative and stereotyped behaviour. Prog Neurobiol. 44, 221-231 
  25. Salgado-Pineda, P., P. Delaveau, O. Blin, and A. Nieoullon. 2005. Dopaminergic contribution to the regulation of emotional perception. Clin. Neuropharmacol. 28, 228-237 
  26. Schluter, O. M., F. Schmitz, R Jahn, C. Rosenmund, and T. C. Sudhof. 2004. A complete genetic analysis of neuronal Rab3 function. J. Neurosci. 24, 6629-6637 
  27. Schoch, S., P. E. Castillo, T. Jo, K. Mukherjee, M. Geppert, Y Wang, F. Schmitz, R. C. Malenka, and T. C. Sudhof. 2002. RIMlalpha forms a protein scaffold for regulating neurotransmitter release at the active zone. Nature 415, 321-326 
  28. Schoch, S., T. Mittelstaedt, P. S. Kaeser, D. Padgett, N. Feldmann, V. Cheval eyre, P. E. Castillo, R E. Hammer, W. Han, F. Schmitz, W. Lin, and T. C. Sudhof. 2006. Redundant functions of RIMlalpha and RIM2alpha in Ca(2+)-triggered neurotransmitter release. EMBO J. 25, 5852-5863 
  29. Seamans, J. K. and C. R Yang. 2004. The principal features and mechanisms of dopamine modulation in the prefrontal cortex. Prog. NeurobioI. 74, 1-58 
  30. Sudhof, T. C. 2004. The synaptic vesicle cycle. Annu. Rev. Neurosci. 27, 509-547 
  31. Sun, L P. Bronk, X. Liu, W. Han, and T. C. Sudhof. 2006. Synapsins regulate use-dependent synaptic plasticity in the calyx of Held by a Ca2+ / calmodulin-dependent pathway. Proc. NatI. A cad. Sci. USA 103, 2880-2885 
  32. Waites, C. L., A. Mehta, P. K. Tan, G. Thomas, R. H. Edwards, and D. E. Krantz. 2001. An acidic motif retains vesicular monoamine transporter 2 on large dense core vesicles. J. Cell BioI. 152, 1159-1168 
  33. Westerink, R. H. 2004. Exocytosis: using amperometry to study presynaptic mechanisms of neurotoxicity. NeurotoxicoIogy 25, 461-470 

이 논문을 인용한 문헌 (0)

  1. 이 논문을 인용한 문헌 없음

원문보기

원문 PDF 다운로드

  • ScienceON :
  • KCI :

원문 URL 링크

원문 PDF 파일 및 링크정보가 존재하지 않을 경우 KISTI DDS 시스템에서 제공하는 원문복사서비스를 사용할 수 있습니다. (원문복사서비스 안내 바로 가기)

상세조회 0건 원문조회 0건

DOI 인용 스타일