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How Ephexin Signaling Promotes Neuronal Stability

Ephexin 信号如何促进神经元稳定性

基本信息

批准号：
7652330
负责人：
CARL ANDREW FRANK
金额：
$ 8.54万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-15 至 2010-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7652330
关键词：
Affect Antibodies Binding Biochemical Biological Assay Calcium Channel Commit Cyclin-Dependent Kinase 5 Data Disease Drosophila genus Environment Eph Family Receptors EphA Receptors Equilibrium Faculty Family Fellowship Fibroblast Growth Factor Receptors Financial compensation G-Protein-Coupled Receptors GTP-Binding Proteins Goals Growth Cones Guanine Nucleotide Exchange Factors Guanosine Triphosphate Phosphohydrolases Homeostasis Homologous Gene Institution Laboratories Lead Ligands Link Mediating Mentors Modeling Molecular Mutation Nervous system structure Neuromuscular Junction Neurons Neurophysiology - biologic function P-Q type voltage-dependent calcium channel Pathway interactions Phase Play Positioning Attribute Protein Kinase C Proteins Publishing Reagent Regulation Research Research Personnel Role Signal Pathway Signal Transduction Signaling Molecule Staining method Stains Structure Synapses Synaptic Transmission System Testing Training Vertebrates Work base design ephexin interest meetings member nervous system disorder neuroregulation neurotransmission presynaptic programs public health relevance relating to nervous system research study retinal rods rho rho GTP-Binding Proteins src-Family Kinases yeast two hybrid system

项目摘要

DESCRIPTION (provided by applicant): The causes and progression of several neurological diseases are influenced by factors that control the stability of neural function. Yet the mechanisms that dictate neural excitation and inhibition are poorly understood. Many studies indicate that homeostatic signaling mechanisms participate in the regulation of neural function - in paricular by modulating the strength of synaptic connections. This proposal aims to clarify the mechanisms of synaptic homeostatic signaling. Prior work defined a role for a presynaptic CaV2.1 calcium channel in synaptic homeostasis. New data show that the cytoplasmic signaling molecule, Ephexin, is also essential for synaptic homeostasis, and it may act via CaV2.1 regulation. In vertebrates, the Ephrin ligand and EphA receptor act upstream of Ephexin, and Rho-type GTPases act downstream of Ephexin to control growth cone dynamics. We hypothesize that all of these molecules are involved in a homeostatic signaling pathway in the presynaptic neuron. The proposed experiments for the K99 mentored phase will test this hypothesis. The results should define the role Ephexin signaling plays in the context of synaptic homeostasis. For the ROD independent phase, candidate molecules already known to regulate calcium channel function and Eph/Ephexin/GTPase signaling will be tested for roles in synaptic homeostasis. The long-term goal of this research is to define signaling mechisms with direct relevance to the cause and progression of neural disease. CANDIDATE: The K99 portion of this reserach will be conducted in the laboratory of Dr. Graeme W. Davis at UCSF. In this environment, I will continue to augment my training, both in the lab as well as in seminars, professional meetings, and one-on-one meetings with UCSF faculty. I am committed to attaining a faculty position at a major research institution. As an independent investigator, I would like to continue my research into the regulation of neural activity. PUBLIC HEALTH RELEVANCE: Many neurological diseases result from nervous system instability, but it is not understood exactly how neural stability is normally maintained. Data show that a molecule called Ephexin helps to direct neural stability. This proposal is designed to clarify exactly how Ephexin performs this function; the results may ultimately lead to a better understanding of the cause, progression, and treatment of neural diseases.

描述（由申请人提供）：