Abnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A)
Abnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A)
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DOI：
10.1073/pnas.96.26.15268
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发表时间：
1999-12-21
影响因子：
11.1
通讯作者：
Bajjalieh, SM
中科院分区：
文献类型：
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作者：
Crowder, KM;Gunther, JM;Bajjalieh, SM
突触囊泡蛋白2（Synaptic vesicle protein 2，SV 2）是突触囊泡和内分泌囊泡共同的膜糖蛋白。与许多参与突触胞吐的蛋白质不同，SV 2在酵母中没有同源物，这表明它在高等真核生物中执行独特的分泌功能。虽然SV 2的结构和蛋白质相互作用提示了多种可能的功能，但其在突触事件中的作用仍然未知。为了探索SV 2在体内环境中的功能，我们通过使用靶向基因破坏产生了不表达主要SV 2同种型SV 2A的小鼠。SV 2A基因破坏的纯合子动物在出生时表现正常。然而，它们不能生长，经历严重的癫痫发作，并在3周内死亡，表明多种神经和内分泌缺陷。海马CA 3区自发抑制性神经传递的电生理研究表明，SV 2A的丢失导致动作电位依赖性γ-氨基丁酸（GABA）能神经传递的减少。相反，动作电位非依赖性神经传递是正常的。突触超微结构的分析表明，神经传递的改变不是由突触密度或形态的变化引起的。这些发现表明，SV 2A是一种必需蛋白，并暗示它在控制胞吐。
Synaptic vesicle protein 2 (SV2) is a membrane glycoprotein common to all synaptic and endocrine vesicles. Unlike many proteins involved in synaptic exocytosis, SV2 has no homolog in yeast, indicating that it performs a function unique to secretion in higher eukaryotes. Although the structure and protein interactions of SV2 suggest multiple possible functions, its role in synaptic events remains unknown. To explore the function of SV2 in an in vivo context, we generated mice that do not express the primary SV2 isoform, SV2A, by using targeted gene disruption. Animals homozygous for the SV2A gene disruption appear normal at birth. However, they fail to grow, experience severe seizures, and die within 3 weeks, suggesting multiple neural and endocrine deficits, Electrophysiological studies of spontaneous inhibitory neurotransmission in the CA3 region of the hippocampus revealed that loss of SV2A leads to a reduction in action potential-dependent gamma-aminobutyric acid (GABA)ergic neurotransmission. In contrast, action potential-independent neurotransmission was normal. Analyses of synapse ultrastructure suggest that altered neurotransmission is not caused by changes in synapse density or morphology. These findings demonstrate that SV2A is an essential protein and implicate it in the control of exocytosis.