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Choline Transporter-Like proteins and the regulation of lipid metabolism during myelination

胆碱转运蛋白样蛋白与髓鞘形成过程中脂质代谢的调节

基本信息

批准号：
9182628
负责人：
Patrice Maurel
金额：
$ 19.38万
依托单位：
RUTGERS THE STATE UNIV OF NJ NEWARK
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9182628
关键词：
1-Phosphatidylinositol 3-Kinase Ammonium Animal Model Apoptosis Axon Binding Cell Adhesion Molecules Cell Communication Cell Differentiation process Cell membrane Cell physiology Cells Charcot-Marie-Tooth Disease Charge Cholesterol Choline Chromatography Communication Corpus Callosum Dependence Development Diet Diglycerides Disease Exhibits Fatty Acids Galactosylceramides Genes Goals Homeostasis In Vitro Lecithin Ligand Binding Lipids Maintenance Mammalian Cell Mass Spectrum Analysis Membrane Membrane Transport Proteins Metabolic Diseases Metabolism Molecular Multiple Sclerosis Mus Myelin Myelin Sheath Nervous system structure Neuroglia Neurons Nutrient Oligodendroglia Optic Nerve PTEN gene Pathway interactions Phosphatidic Acid Phosphatidylcholine Biosynthesis Phosphatidylinositols Phosphoric Monoester Hydrolases Production Property Proteins RNA Splicing Recruitment Activity Regulation Schwann Cells Signal Pathway Signal Transduction Specificity Sphingomyelins System Therapeutic Intervention Time Variant Vesicle Western Blotting base cell growth choline transporter in vivo knock-down lipid biosynthesis lipid metabolism myelination nervous system disorder neuropathology oligodendrocyte myelination phosphoinositide-3,4,5-triphosphate receptor sciatic nerve trafficking

项目摘要

ABSTRACT This proposal focuses on the function of Choline Transporter CTL1 in regulating myelination by oligodendrocytes (CNS) and Schwann cells (PNS). Choline is important in the biosynthesis of phosphatidylcholine, a major lipid in myelin. It is the direct precursor of sphingomyelin, another major myelin lipid, It is also involved in the homeostatic regulation of important signaling components that have a direct implication on the initiation of myelination, the compaction of the myelin sheath and myelin maintenance. Necl4 is a cell adhesion molecule that is required for PNS myelination. Its knockdown in an animal model induces the formation of myelin abnormalities that are the hallmarks of Charcot-Marie-Tooth neuropathologies. We recently found that Necl4 interacts with CTL1, and regulates choline transport, homeostasis, and downstream Choline-derivatives. It is unclear how myelinating glial cells regulate their metabolism at the onset of myelination to respond to the high demand in lipids needed for plasma membrane production, without disrupting other cell processes. The Necl4/CTL1 interaction suggests that CTL1 is an important component of the regulation. The overall goal of this proposal is to understand the regulation of choline transport in myelinating cells, and the impact of its deregulation on myelin formation and maintenance.

摘要该建议集中于胆碱转运蛋白CTL 1在调节髓鞘形成中的功能，少突胶质细胞（CNS）和雪旺细胞（PNS）。胆碱在磷脂酰胆碱的生物合成中是重要的，磷脂酰胆碱是髓鞘中的主要脂质。是鞘磷脂的直接前体，另一种主要的髓鞘脂质，它也参与体内平衡调节重要的信号成分，这些信号成分对启动具有直接影响，髓鞘形成、髓鞘的致密化和髓鞘的维持。 Necl 4是PNS髓鞘形成所需的细胞粘附分子。它在动物身上的击倒模型诱导形成髓鞘异常，这是腓骨肌萎缩症的标志神经病理学我们最近发现Necl 4与CTL 1相互作用，调节胆碱转运，稳态和下游胆碱衍生物。目前尚不清楚髓鞘形成胶质细胞如何在髓鞘形成开始时调节其代谢，响应质膜生产所需的脂质的高需求，而不干扰其他细胞突起Necl 4/CTL 1相互作用表明CTL 1是Necl 4/CTL 1相互作用的重要组分。调控这个建议的总体目标是了解髓鞘形成过程中胆碱转运的调节细胞，以及其失调对髓鞘形成和维持的影响。