Presynaptic cytomatrix proteins and synaptogenesis

哺乳动物中枢神经系统的突触是高度专门化的细胞连接，设计用于神经细胞和它们的靶细胞之间快速和调节的信号传递。发育中的中枢神经系统中的突触发生和突触重组异常与脆性X、癫痫、精神分裂症和智力低下等发育障碍密切相关。我们要了解不同的遗传和环境侮辱是如何导致认知功能障碍和智力低下的，需要更好地理解导致中枢神经系统突触正确组装和功能的细胞机制。这需要对突触连接的组成以及神经元用来正确分类流量和定位每个组成部分的机制进行分子描述。我们对中枢神经系统突触的研究导致了许多突触连接蛋白的鉴定和表征。最近发现的Bason是在活动区组装的突触前细胞骨架基质的一种新成分。根据其结构和分布，我们推测它可能参与了中枢神经系统突触的组装和功能。关于智力低下和认知功能障碍，我们对Bason基因及其转录本的分析表明，存在与Huntingtin、ataxins和脆性X智力低下类似的CAG扩展。此外，在神经退行性疾病、多系统萎缩中，Basson的表达选择性增强。为了深入了解巴松管在突触前细胞骨架中所起的作用，我们建议研究巴松管在中枢神经系统突触的运输和组装的指导机制。此外，我们还建议通过分析小鼠巴松管基因BSN功能突变对发育中的小鼠脑中中枢神经系统突触的结构、组装和功能的影响来评估巴松管在突触前神经末梢的功能。

Synapses of the mammalian CNS are highly specialized cellular junctions designed for rapid and regulated signaling between nerve cells and their targets. Abnormal synaptogenesis and synaptic reorganization in the developing CNS has been strongly correlated with developmental disorders such as fragile X, epilepsy, schizophrenia and mental retardation. Our ability to understand how different genetic and environmental insults cause cognitive dysfunction and mental retardation requires a better understanding of the cellular mechanisms that lead to the proper assembly and function of CNS synapses. This requires a molecular description of the constituents of synaptic junctions and the mechanisms used by neurons to correctly sort traffic and localized each component. Our studies of CNS synapses have led to the identification and characterization of numerous synaptic junctional proteins. One of the most recently identified, Bassoon, is a novel component of the presynaptic cytoskeletal matrix assembled at the active zone. Based on its structure on its structure and distribution, we hypothesize that it is involved in the assembly and function of CNS synapses. With regard to mental retardation and cognitive dysfunction, our analysis of the Bassoon gene and its transcripts have revealed the presence of a CAG expansion similar to these found Huntingtin, Ataxins and the Fragile X mental retardation Moreover, Basson expression is selectively enhance in a neurodegenerative disorder, multiple system atrophy. To gain insights into the role played by Bassoon in the presynaptic cytoskeletal matrix, we proposed to examine the mechanisms directing that transport and assembly of Bassoon at CNS synapses In addition we propose to assess the function of Bassoon in presynaptic nerve terminals by analyzing loss of function mutations in the mouse Bassoon gene Bsn on the structure, assembly, and function of CNS synapses in the developing mouse brain.