DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Kim, Eunjoon | - |
dc.contributor.advisor | 김은준 | - |
dc.contributor.author | Lee, Dongwon | - |
dc.contributor.author | 이동원 | - |
dc.date.accessioned | 2017-03-29T02:44:28Z | - |
dc.date.available | 2017-03-29T02:44:28Z | - |
dc.date.issued | 2016 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=648150&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/222089 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 생명과학과, 2016.2 ,[vii, 78 p. :] | - |
dc.description.abstract | Long-term synaptic plasticity is controlled by balanced actions of positive and negative regulators at synapses. Protein kinase $C_\alpha$ ($PKC_\alpha$) is a critical mediator that induces long-term depression (LTD) at cerebellar parallel fiber-Purkinje cell synapses. However, the precise regulation of $PKC_\alpha$ for LTD is not well understood. Here, I investigated the role of diacylglycerol kinase $\zeta$ (DGK$\zeta$) - a kinase that physically interacts with $PKC_\alpha$ as well as postsynaptic density protein 95 (PSD-95) family proteins and functionally inhibits $PKC_\alpha$ by metabolizing diacylglycerol (DAG) - in the regulation of cerebellar LTD. In Purkinje cells of DGK$\zeta$-deficient mice, LTD was impaired and $PKC_\alpha$ was less localized in dendrites and synapses. This impaired LTD was rescued by virus-mediated expression of wild-type DGK$\zeta$, but not by a kinase-dead mutant DGK$\zeta$ or a mutant lacking the ability to localize at synapses, indicating that both the kinase activity and synaptic anchoring functions of DGKζ are required for LTD. In addition, experiments using another DGK$\zeta$ mutant as well as immunoprecipitation analysis revealed an inverse regulatory mechanism, in which $PKC_\alpha$ phosphorylates, inactivates, and then is dissociated from DGK$\zeta$, is required for LTD. These results indicate that DGK$\zeta$ is targeted to synapses, through its interaction with PSD-95 family proteins, to facilitate synaptic localization of $PKC_\alpha$, but maintains $PKC_\alpha$ in a minimally activated state by reducing local DAG until its activation and release from DGK$\zeta$ during LTD. Such local and reciprocal regulation of positive and negative regulators may contribute to the fine tuning of synaptic signaling. | - |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | cerebellum | - |
dc.subject | long-term depression | - |
dc.subject | Purkinje cells | - |
dc.subject | DGK$\zeta$ | - |
dc.subject | 소뇌 | - |
dc.subject | 시냅스가소성 | - |
dc.subject | 소뇌 장기저하 | - |
dc.subject | 퍼킨지 세포 | - |
dc.subject | 디아실글리세롤인산화효소 | - |
dc.title | Role of diacylglycerol kinase $\zeta (DGK \zeta)$ in the regulation of cerebellar purkinje cell synapses | - |
dc.title.alternative | diacylglycerol kinase $\zeta (DGK \zeta)$ 에 의한 소뇌 퍼킨지 세포 시냅스 조절에 관한 연구 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :생명과학과, | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.