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: 6182760
• 负责人: HAL A SKOPICKI
• 金额: $ 12.02万
• 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/6182760
• 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 (根据申请者摘要改编)申请者获得了细胞博士学位 生理学，并在临床医学和心脏病学培训后，开始 分子生物学博士后研究。该MCSD奖项将支持 分子和细胞生物学博士后中后期培训 以便他能过渡到独立调查员。分部 哥伦比亚长老会医学中心的循环生理学已经承诺 90%的时间都投入到基础科学研究中。 本应用程序的目标是促进对 支配胚胎肌的分子信号转导途径 发育，特别是细胞凋亡。总体的工作假设是 横纹肌的胚胎发育需要预先确定的 消除原始体节和成肌细胞，部分是由 通过IP3受体。工作计划在授奖期间开始。 并继续调查人员的独立性。研究由The Mentor发现IP3受体在横纹肌细胞中表达 并在T细胞凋亡信号转导中发挥重要作用。先前的研究 申请者和导师注意到：1)发育中的体节中的细胞凋亡 和体内成熟的肌细胞；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)IP3受体密度增加 在体节和指间易发生凋亡的区域内； IP3受体在成肌细胞中的过表达导致细胞抑制 体外融合。这些数据表明IP3和IP3之间存在因果关系。 受体表达与成肌细胞早期分化和凋亡。 因此，这个项目的具体目标是为了测试 假说：1)肌肉发生涉及一种有序的凋亡模式 躯体和肢体，2)躯体和指间肢体的IP3受体 成肌细胞分别定义原始细胞和成熟的成肌细胞， 注定要经历细胞凋亡；3)IP3受体很重要 调控生肌的细胞内钙离子决定因素 分化和细胞凋亡。 该网络的阐明将进一步加深对纹状体的认识。 肌肉发育调控与成肌细胞凋亡的命运。Dr。 斯科皮基将由分子中心主任安德鲁·马克斯博士指导 他是心脏病学专家，肌肉细胞转录和分子生物学方面的专家。 哥伦比亚大学内科医生和外科医生学院提供 良好的学术环境，既有基础科学方面的培训，也有 理论和实验。