2017-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/702402摘要：生物體必須藉著神經系統來感知環境的訊息，記憶經驗，思考解決方案，完成各種反應。神經細胞是神經系統的基本單元，神經細胞的功能需要有特殊極性化的構造來從正確來源接收與處理訊息，並傳送訊息到正確的標的上。本計畫主要目的在了解突觸前構造分子presynaptic components（如突觸小泡、活性區蛋白）如何能夠準確地分布在正確的軸突位置上以形成具有功能的神經迴路。在線蟲C.elegans 的DA9 神經細胞上，我們已經發現了兩個cyclin-dependent kinases (CDKs) (CDK-5 與PCT-1/CDK-16) 能夠控制presynaptic components 在神經細胞中的分佈。在本計畫中，我們將會研究CDK-5 與 PCT-1 對調控presynaptic components 的分子機制，還有環境訊號如何改變CDK-5 與 PCT-1的活性。藉由遺傳篩檢與序列分析，我們成功找到cAMP/PKA pathway，AP1 clathrin adaptor complex，與Netrin pathway 的基因參予在CDKs 對於突觸形成的調控過程中。我們將採用一系列遺傳與功能分析來瞭解這些基因在CDK-5 與 PCT-1 訊息傳遞路徑的角色，而即時影像分析與曠時攝影將幫助我們進一步瞭解CDK-5 與 PCT-1 如何控制極性化的突觸運送與突觸穩定。<br> Abstract: The neuron is the basic unit of the nervous system, which allows organisms to sense, memorize, think,and respond to the world. The function of the neuron relies on its proper polarization andcompartmentalization in order to receive signals from the right field, process information, and transmit it tothe correct target. The focus of this proposal is to understand the molecular mechanisms underlying howpresynaptic components like synaptic vesicles (SVs) and active zone proteins are localized to defined axonaldomains. Utilizing the motor neuron DA9 in C. elegans as my model system, we discovered that twocyclin-dependent kinases (CDKs), CDK-5 and PCT-1/CDK-16, and their specific activators p35/CDKA-1and CYY-1 respectively are key regulators for localizing presynaptic components. Here, we propose tocharacterize how CDK-5 and PCT-1 regulate the polarized localization of presynaptic components and howenvironmental cues direct these two kinases. By candidate research and a forward genetic screen, we havefound that the cAMP/PKA pathway, the AP1 clathrin adaptor complex, and Netrin pathway are veryimportant regulators of CDKs in controlling synapse formation. We will perform a series of geneticinteraction and functional analysis experiments to clarify the role of these genes in the CDK-5 and PCT-1pathways. Further characterization by real-time synaptic vesicle transport recordings and time-lapsephotoactivation experiments on synaptic structures will manifest the specific roles of the CDK-5 and PCT-1pathways on synaptic polarized trafficking and synapse stability.