Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Rim1α and Neurexin3 Regulate Synaptosomal Dopamine Release

Rim1α와 neurexin3의 시냅토좀 도파민 분비 조절

  • Lee, Sang-Kyeong (Department of Neuropsychiatry, College of Medicine, Inje University) ;
  • Shim, Joo-Cheol (Department of Neuropsychiatry, College of Medicine, Inje University) ;
  • Kim, Young-Hoon (Department of Neuropsychiatry, College of Medicine, Inje University) ;
  • Kong, Bo-Geum (Department of Neuropsychiatry, College of Medicine, Inje University) ;
  • Seog, Dae-Hyun (Department of Biochemistry, College of Medicine, Inje University)
  • 이상경 (인제대학교 의과대학 신경정신과학교실) ;
  • 심주철 (인제대학교 의과대학 신경정신과학교실) ;
  • 김영훈 (인제대학교 의과대학 신경정신과학교실) ;
  • 공보금 (인제대학교 의과대학 신경정신과학교실) ;
  • 석대현 (인제대학교 의과대학 생화학교실)
  • Published : 2009.09.30
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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.

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.

Keywords

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