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Galectin Modulation of Glutamate Receptors and Neuronal Function

半乳糖凝集素对谷氨酸受体和神经元功能的调节

基本信息

批准号：
8609085
负责人：
GEOFFREY T SWANSON
金额：
$ 32.89万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-02-01 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8609085
关键词：
Acute Affinity Animals Behavior Binding Binding Proteins Brain Brain Neoplasms Cell Surface Proteins Cell Survival Cell membrane Characteristics Chronic Complement Complex Cytoplasm Dendritic Cells Dendritic Spines Development Disaccharides Exposure to Extracellular Matrix Family Galactose Binding Lectin Galactosides Galectin 1 Glioma Glutamate Receptor Glycoproteins Golgi Apparatus Hippocampus (Brain)Human Immune system Induction of Apoptosis Integrins Investigation Lectin Ligand Binding Domain Long-Term Potentiation MAP Kinase Gene Malignant neoplasm of brain Mediating Membrane Molecular Morphology Multiple Sclerosis Mus N-acetyllactosamine Neoplasm Metastasis Nerve Degeneration Nervous system structure Neurodegenerative Disorders Neuroglia Neurologic Neurons Oligosaccharides Pathway interactions Peripheral Phosphotransferases Physiological Polysaccharides Preparation Process Protein Family Proteins Recombinants Research Role Signal Pathway Signal Transduction Signaling Molecule Site Slice Structure Synapses Synaptic Transmission Synaptic plasticity System Testing Transducers Vascularization Wound Healing angiogenesis base cancer cell cell type crosslink density desensitization insight kainate knowledge base member neurogenesis neuronal excitability neurotransmission novel public health relevance receptor receptor function research study sugar synthetic enzyme tool

项目摘要

DESCRIPTION (provided by applicant): The purpose of this project is to understand the role of animal-derived lectins in nervous system activity. Investigation into the neuronal activities of galectins, a family of mammalian soluble galactoside-binding proteins, thus far has focused primarily on how they impact neurogenesis or act as metastatic factors for brain cancer cells. However, galectins also are known to be secreted by glia and neurons in the mature nervous system, and therefore are likely to have a physiological role in brain function. We hypothesize that galectins impact neuronal function through short-term morphological changes in dendritic spines, alterations in synaptic plasticity, and reductions in neuronal viability. These activities re mediated by engagement of intracellular signaling cascades that include ERK/MAPK. Integral proteins expressed on neuronal plasma membranes typically contain the glycan N acetyllactosamine, a common disaccharide constituent of complex oligosaccharides, and therefore could serve as targets for galectin binding and cross-linking of signaling molecules, leading to their activation and initiation of intracellular enzymatic cascades. In addition to thei actions on neurons, galectins are useful tools for understanding the relevance of N-glycans to ionotropic glutamate receptor (iGluR) function due to their allosteric modulatory actions. Accordingly, the proposed project will elucidate how galectins impact neuronal function and viability and use these proteins as glycan-specific tools in structure-function studies with recombinant iGluRs. In Specific Aim 1, we will examine galectin activity on neurotransmission and synaptic plasticity in the mouse hippocampus. Experiments in Specific Aim 2 will test the hypothesis that galectins alter neuronal structural plasticity through intracellular kinase cascades. Finally, in Specific Aim 3, we will determine the spectrum of galectin actions on iGluRs and their molecular basis. We will probe the physical characteristics of galectins that optimize their functional action on iGluRs. These studies will yield insight into the as-yet unexplored relevance of galectins to neuronal function, which also will be relevant to understanding their importance to glioma-induced alterations in neuronal excitability.

描述（由申请人提供）：本项目的目的是了解动物源性凝集素在神经系统活动中的作用。神经活动的研究