IP3 RECEPTOR MEDIATED APOPTOSIS DURING MYOGENESIS

肌生成过程中 IP3 受体介导的细胞凋亡

• 批准号: 2592358
• 负责人: HAL A SKOPICKI
• 金额: $ 8.55万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-06 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2592358
• 关键词: apoptosis; biological signal transduction; calcium flux; inositol phosphates; laboratory mouse; mammalian embryology; muscle cells; myoblasts; myogenesis; receptor; receptor expression

DESCRIPTION (Adapted from applicants' abstract) The applicant received a Ph.D. in cell physiology and, after clinical medicine and cardiology training, began post-doctoral work in molecular biology. This MCSD award will support mid-to-later stages of post-doctoral training in molecular and cell biology to allow for his transition to an independent investigator. The Division of Circulatory Physiology at Columbia-Presbyterian Medical Center has committed 90% of his time to basic science research. The goal of this application is to advance the understanding of the molecular signal transduction pathways that govern embryologic muscle development, specifically apoptosis. The overall working hypothesis is that embryonic development of striated muscle requires the predetermined elimination of primordial somites and myoblasts that is mediated, in part, via the IP3 receptor. Work is planned to begin during the term of the award and continue through independence of the investigator. Studies by the mentor have shown that IP3 receptors are expressed in striated muscle cells and also play a critical role in T cell apoptotic signaling. Prior studies by the applicant and mentor note: 1) Apoptosis within developing somites and maturing myocytes in vivo; 2) The ability to label the myogenic lineage via a novel homeodomain protein; 3) An increase in IP3 receptor density within somites and interdigital regions prone to apoptosis; and 4) Overexpression of IP3 receptors in myoblasts causes inhibition of cell fusion in vitro. These data suggest a causal relationship between IP3 receptor expression and incipient myoblast differentiation and apoptosis. Therefore, the specific aims of this project are designed to test the hypotheses that: 1) Myogenesis involves an ordered pattern of apoptosis in somites and limbs, 2) IP3 receptors of somitic and interdigital limb myoblasts define primordial cells and maturing myoblasts, respectively, destined to undergo apoptosis; and 3) IP3 receptors are important determinants of intracellular calcium which regulates myogenic differentiation and apoptosis. The elucidation of this network will further the understanding of striated muscle developmental regulation and the fate of apoptotic myoblasts. Dr. Skopicki will be mentored by Dr. Andrew Marks, the Director of Molecular Cardiology and an expert in muscle cell transcription and molecular biology. The College of Physicians and Surgeons of Columbia University affords an outstanding academic environment for training in both basic scientific theory and experimentation.

描述 （摘自申请人摘要）申请人获得博士学位。在细胞 在临床医学和心脏病学培训之后， 从事分子生物学的博士后工作。 该MCSD奖将支持 分子和细胞生物学博士后培养中后期 让他转型为独立调查员 司 哥伦比亚长老会医学中心的循环生理学 他90%的时间用于基础科学研究。 这个应用程序的目标是促进对 控制胚胎肌肉的分子信号转导途径 发展，特别是凋亡。 总的工作假设是， 横纹肌的胚胎发育需要预先确定的 原始体节和成肌细胞的消除，部分地， 通过IP 3受体。 工程计划在授标期内开始 并通过独立调查员继续进行。 的研究报告 Mentor已经表明IP 3受体在横纹肌细胞中表达， 并且在T细胞凋亡信号传导中也起关键作用。 先前研究 由申请人和导师注释：1）发育体节内的细胞凋亡 2）标记肌源性谱系的能力 通过一种新的同源结构域蛋白; 3）IP 3受体密度的增加 在体节和易于凋亡的趾间区域内;和4） 成肌细胞IP 3受体过表达导致细胞增殖抑制 体外融合 这些数据表明，IP 3 受体表达和早期成肌细胞分化和凋亡。 因此，本项目的具体目标是测试 假设：1）肌发生涉及细胞凋亡的有序模式， 体节和趾间肢的IP 3受体 成肌细胞分别定义原始细胞和成熟成肌细胞， 注定要经历细胞凋亡;和3）IP 3受体是重要的 调节肌原性的细胞内钙决定簇 分化和凋亡。 对这一网络的阐明将进一步加深对横纹肌的理解 肌肉发育调节和凋亡成肌细胞的命运。 博士 Skopicki将由分子生物学主任Andrew Marks博士指导 心脏病学和肌肉细胞转录和分子生物学专家。 哥伦比亚大学的内科医生和外科医生学院提供了一个 优秀的学术环境，培养基础科学和 理论和实验。