Synapsins: Structure and Function in Neurotransmission

描述（由申请人提供）：神经系统执行复杂任务（如感觉知觉、学习和协调运动）的能力依赖于化学突触神经递质的动态释放。神经递质的分泌涉及突触囊泡运输到神经末梢质膜的严格调控过程，在那里它们融合并释放神经递质到突触后受体。突触动力学调节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起作用。本提案的目标是进一步阐明突触的功能。目的1将探讨突触蛋白I和突触蛋白II的不同功能，以及它们的功能是否通过影响ATP结合的突变依赖于ATP。Aim II将确定蛋白激酶A对突触蛋白的磷酸化对于突触小泡进入“易释放”状态是否必要。Aim III将确定保守的突触蛋白E结构域和与该结构域结合的蛋白的功能。了解蛋白质在神经传递中的功能可能有助于阐明与突触功能障碍相关的疾病的原因。

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.