Defective glycinergic synaptic transmission in zebrafish motility mutants.
Defective glycinergic synaptic transmission in zebrafish motility mutants.
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DOI：
10.3389/neuro.02.026.2009
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发表时间：
2009
影响因子：
4.8
通讯作者：
Kuwada JY
中科院分区：
文献类型：
--
作者：
Hirata H;Carta E;Yamanaka I;Harvey RJ;Kuwada JY
甘氨酸是脊髓和脑干中的主要抑制性神经递质。最近，利用分子遗传学对斑马鱼的甘氨酸突触传递进行体内分析。 ENU 诱变筛选发现了两种甘氨酸突触传递缺陷的行为突变体。斑马鱼 bandoneon (beo) 突变体的 glrbb 存在缺陷，glrbb 是重复的甘氨酸受体 (GlyR) β 亚基基因之一。由于缺乏 GlyR 突触聚集，这些突变体表现出甘氨酸能突触传递的损失。由于脊髓两侧运动回路的相互抑制随之丧失，两侧的运动神经元同时激活，导致beo突变体的轴向肌肉双侧收缩，引发所谓的“手风琴”表型。在几种哺乳动物中观察到 GlyR 亚基基因的类似缺陷，这是人类惊厥过度/惊吓症的基础。相比之下，斑马鱼休克（sho）突变体在编码GlyT1的slc6a9中存在缺陷，GlyT1是一种甘氨酸转运蛋白，由后脑和脊髓中甘氨酸突触周围的星形胶质细胞表达。 GlyT1 介导从突触间隙快速摄取甘氨酸，终止突触传递。在斑马鱼 sho 突变体中，细胞外甘氨酸似乎升高，导致突触后神经元持续受到抑制，随后运动性降低，从而导致“抽搐一次”表型。我们回顾了有关斑马鱼“手风琴”和“一次抽搐”突变体（包括 beo 和 sho）的现有知识，并报告了一个新的 α2 亚基的鉴定，该亚基修改了斑马鱼 GlyR 的系统发育。
Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Recently, in vivo analysis of glycinergic synaptic transmission has been pursued in zebrafish using molecular genetics. An ENU mutagenesis screen identified two behavioral mutants that are defective in glycinergic synaptic transmission. Zebrafish bandoneon (beo) mutants have a defect in glrbb, one of the duplicated glycine receptor (GlyR) β subunit genes. These mutants exhibit a loss of glycinergic synaptic transmission due to a lack of synaptic aggregation of GlyRs. Due to the consequent loss of reciprocal inhibition of motor circuits between the two sides of the spinal cord, motor neurons activate simultaneously on both sides resulting in bilateral contraction of axial muscles of beo mutants, eliciting the so-called ‘accordion’ phenotype. Similar defects in GlyR subunit genes have been observed in several mammals and are the basis for human hyperekplexia/startle disease. By contrast, zebrafish shocked (sho) mutants have a defect in slc6a9, encoding GlyT1, a glycine transporter that is expressed by astroglial cells surrounding the glycinergic synapse in the hindbrain and spinal cord. GlyT1 mediates rapid uptake of glycine from the synaptic cleft, terminating synaptic transmission. In zebrafish sho mutants, there appears to be elevated extracellular glycine resulting in persistent inhibition of postsynaptic neurons and subsequent reduced motility, causing the ‘twitch-once’ phenotype. We review current knowledge regarding zebrafish ‘accordion’ and ‘twitch-once’ mutants, including beo and sho, and report the identification of a new α2 subunit that revises the phylogeny of zebrafish GlyRs.
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影响因子：
4.5
作者：
Dowling, James J.;Vreede, Andrew P.;Low, Sean E.;Gibbs, Elizabeth M.;Kuwada, John Y.;Bonnemann, Carsten G.;Feldman, Eva L.
通讯作者：
Feldman, Eva L.
影响因子：
16.2
作者：
BECKER, CM;SCHMIEDEN, V;BETZ, H
通讯作者：
BETZ, H
影响因子：
2.7
作者：
Davidson, AE;Balciunas, D;Ekker, SC
通讯作者：
Ekker, SC
影响因子：
25
作者：
Behra, M;Cousin, X;Strähle, U
通讯作者：
Strähle, U
影响因子：
2.7
作者：
AMSTERDAM, A;LIN, S;HOPKINS, N
通讯作者：
HOPKINS, N