Intracellular trafficking of long chain fatty acyl-CoAs

长链脂肪酰辅酶A的细胞内运输

• 批准号: 6887712
• 负责人: HEATHER A HOSTETLER
• 金额: $ 4.83万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6887712
• 关键词: acyl coA; cell nucleus; fatty acid binding protein; genetic regulation; genetic transcription; intracellular transport; laboratory mouse; lipid transport; long chain fatty acid; peroxisome proliferator activated receptor; postdoctoral investigator; protein binding

DESCRIPTION (provided by applicant): Although recent data suggest that the nuclear regulatory protein, PPARalpha, interacts with long chain fatty acyl CoA (LCFACoA), it is unclear whether this represents high affinity binding that is physiologically significant. Little is known regarding the distribution of LCFA-CoA to the nucleus or factors that transport LCFA-CoA to the nucleus for regulating nuclear transcription. Liver cytoplasm is rich in high affinity LCFA-CoA binding proteins, fatty acid binding protein (L-FABP) >> acyl CoA binding protein (ACBP). Transcriptional activation of PPARalpha strongly upregulates L-FABP expression. These data led to the hypothesis that LCFA-CoA binding protein(s) regulate the distribution of LCFA-CoA to the nucleus for interaction with and regulation of PPARalpha transcriptional activity. The specific aims are to: Aim 1. Determine if PPARalpha binds LCFA-CoA with high affinity, in the physiological range of nuclear LCFA-CoA levels. Aim 2. Resolve whether L-FABP regulates LCFA-CoA distribution to the nucleus. Aim 3. Elucidate whether L-FABP directly interacts with PPARalpha in the nucleus.

描述（由申请人提供）：尽管最近的数据表明核调节蛋白PPARALPHA与长链脂肪酰基COA（LCFACOA）相互作用，但尚不清楚这是否代表具有生理意义的高亲和力。关于LCFA-COA在细胞核中的分布或将LCFA-COA转移到调节核转录的细胞核的因素方面，知之甚少。肝细胞质富含高亲和力LCFA-COA结合蛋白，脂肪酸结合蛋白（L-FABP）>>酰基COA结合蛋白（ACBP）。 pParalpha的转录激活强烈上调L-FABP表达。这些数据导致了以下假设：LCFA-COA结合蛋白（S）调节LCFA-COA与细胞核的分布，以与PPARALPHA转录活性的相互作用和调节。具体目的是： AIM 1。确定PPARALPHA是否在核LCFA-COA水平的生理范围内结合具有高亲和力的LCFA-COA。 AIM 2。解决L-FABP是否调节LCFA-COA分布到核。 AIM 3。阐明L-FABP是否直接与核中的pParalpha相互作用。