Multi-Domain Sec14 Proteins and Developmentally Regulated Membrane Morphogenesis

多域 Sec14 蛋白与发育调控的膜形态发生

• 批准号: 7557880
• 负责人: Vytas A Bankaitis
• 金额: $ 27.74万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7557880
• 关键词: Ablation; Actins; Address; Arabidopsis; Binding; Biochemical; Biochemistry; Biological; Biological Process; Carcinoma; Categories; Cell membrane; Cell physiology; Coupled; Cytoskeleton; Data; Defect; Disease; Eukaryota; Exhibits; Genetic; Gold; Growth; Hair; Hair Root; Health; Homeostasis; Human; Image; Inherited; Lipid Binding; Lipids; Mammals; Mediating; Membrane; Membrane Protein Traffic; Microfilaments; Microtubules; Modeling; Molecular; Morphogenesis; Mutagenesis; Nerve Degeneration; Neurons; Neuropathy; Pathway interactions; Phenotype; Phosphatidylinositols; Phospholipids; Phosphotransferases; Plants; Process; Property; Proteins; Regulation; Reporter; Research; Signal Pathway; Signal Transduction; Signaling Protein; Structure; System; Testing; Tissues; Translating; base; falls; in vivo; mutant; nodulin; phosphatidylcholine transfer protein; protein expression; receptor-mediated signaling

DESCRIPTION (provided by applicant): The objective of the proposed research is to undertake a comprehensive functional analysis of an underinvestigated class of proteins: the phosphatidylinositol/ phosphatidylcholine transfer proteins (PITPs). The Sec14-like cabal of the PITP ensemble consists of > 500 proteins, yet remains a poorly studied class of signaling proteins. This is particularly true for multi-domain Sec14-proteins because expression of these proteins is limited to higher eukaryotes and thus less easily amenable to functional analysis using genetic approaches. We recently discovered that Sec14-nodulin and Sec14-GOLD proteins control developmentally regulated pathways for polarized membrane trafficking in Arabidopsis. We will take advantage of the Arabidopsis model to determine how Sec14-nodulin and Sec14-GOLD proteins execute their biological functions. We expect the findings that come from these Arabidopsis studies will translate directly to mammalian systems, and that these studies will clarify essentially uninvestigated questions regarding the mechanism of function of such higher eukaryotic multi-domain Sec14 proteins. From the standpoint of human health, the evidence indicates Sec14-like PITPs regulate the interface between phospholipid-mediated signal transduction processes and diverse cellular processes such as membrane trafficking, actin organization, lipid signaling, receptor-mediated signaling, and neuronal function. As there are several known cases of inherited Sec14-like protein insufficiency in higher eukaryotes that result in neuropathies and carcinomas, the proposed studies will provide new and fundamental information with direct bearing on the molecular mechanisms by which multi-domain Sec14s proteins protect mammals from neurodegenerative and proliferative diseases.

描述（由申请人提供）：拟议的研究的目的是对未经过研究的蛋白质类别进行全面的功能分析：磷脂酰肌醇/磷脂酰胆碱转移蛋白（PITPS）。 PITP合奏的Sec14般的阴谋集由 > 500种蛋白质，但仍然是研究不足的信号蛋白。对于多域SEC14-蛋白质而言，尤其如此，因为这些蛋白的表达仅限于更高的真核生物，因此使用遗传方法不容易对功能分析。我们最近发现，Sec14----------蛋白质控制拟南芥中极化膜运输的发育途径。我们将利用拟南芥模型来确定Sec14----------蛋白如何执行其生物学功能。我们预计这些拟南芥研究的发现将直接转化为哺乳动物系统，并且这些研究将阐明有关如此高的真核多域SEC14蛋白功能机理的基本未评估的问题。从人类健康的角度来看，证据表明Sec14样的PITP调节磷脂介导的信号转导过程与多种细胞过程（例如膜运输，肌动蛋白组织，脂质信号，脂质信号，受体介导的信号传导和神经元功能）之间的界面。由于有几个已知的遗传性sec14样蛋白质不足在高等真核生物中导致神经病和癌症中，因此拟议的研究将提供新的，基本的信息，直接与分子机制有关，通过这些信息，多域Sec14s sec14s蛋白可以保护哺乳动物免受神经变性和增殖性疾病的侵蚀。