Synapsins: Structure and Function in Neurotransmission

描述（由申请人提供）：神经系统执行复杂任务（如感官知觉、学习和协调运动）的能力依赖于化学突触处神经递质的动态释放。神经递质的分泌涉及一个严格调节的过程，将突触囊泡运输到神经末梢的质膜，在那里它们融合并将神经递质释放到突触后受体上。调节突触动力学的一个关键组成部分是神经元控制可融合突触囊泡数量的能力。一个蛋白质家族，突触蛋白，被认为在这种调节中发挥作用。该提案的目标是进一步阐明突触蛋白的功能。目的探讨突触蛋白I和II的不同功能，以及它们的功能是否通过突变影响ATP结合而依赖于ATP。目的二将确定是否磷酸化的突触蛋白的蛋白激酶A是必要的运动突触囊泡进入一个“容易释放”的状态。目的III将确定一个保守的突触素E结构域的功能和蛋白质结合到这个域。了解蛋白质在神经传递中的功能有助于阐明疾病相关的突触功能障碍的原因。

DESCRIPTION (provided by applicant): The ability of the nervous system to perform complex tasks such as sensory perception, learning, and coordinated movement relies on the dynamic release of neurotransmitters at chemical synapses. The secretion of neurotransmitters involves a tightly regulated process of trafficking synaptic vesicles to the plasma membrane of nerve terminals where they fuse and release neurotransmitters onto postsynaptic receptors. A key component in the regulation of synaptic dynamics is the ability of the neuron to control the number of fusable synaptic vesicles. A family of proteins, synapsins, is proposed to play a role in this regulation. This proposal's goal is to further elucidate the function(s) of synapsins. Aim I will address the differential function of synapsin I and II and whether their function is ATP-dependent through mutations affecting ATP binding. Aim II will determine whether phosphorylation of synapsins by protein kinase A is necessary for the movement of synaptic vesicles into a 'readily releasable' state. Aim III will identify a function for the conserved synapsin E domain and proteins that bind to this domain. Knowledge of protein function in neurotransmission may help elucidate the cause of disease related synaptic dysfunction.