Role of IGF-1 receptor in axonal growth

IGF-1 受体在轴突生长中的作用

• 批准号: 6622174
• 负责人: KARL H PFENNINGER
• 金额: $ 4.03万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6622174
• 关键词: South America; antisense nucleic acid; axon; brain derived neurotrophic factor; cell growth regulation; cell membrane; confocal scanning microscopy; cooperative study; enzyme inhibitors; fluorescence microscopy; fluorescent dye /probe; green fluorescent proteins; growth cones; growth factor receptors; hippocampus; immunocytochemistry; immunofluorescence technique; insulinlike growth factor; light microscopy; membrane biogenesis; molecular cloning; neurons; phosphatidylinositol 3 kinase; protein structure function; tissue /cell culture; transposon /insertion element

DESCRIPTION (provided by applicant) Axonal growth cones contain an unusual IGF-1 receptor with an immunochemically distinct B subunit, Bgc. We have demonstrated that BDNF regulates the distal insertion (at the axonal growth cone) of Bgc in hippocampal neurons. We propose that, in turn, IGF-1 regulates plasmalemmal expansion and, thus, neurite growth by controlling the exocytotic insertion of plasmalemmal precursor vesicles (PPVs). We hypothesize further that there are at least three types of PPVs that may be inserted differentially, and that phosphatidylinositol 3-kinase (PI3k) is involved in the regulation of PPV insertion. We propose to: (i) study membrane expansion at the growth cone in our test tube assay, as well as in intact growth cones in culture using a light microscopic strategy; (ii) characterize the properties of different PPV classes separated by immunoisolation; and (iii) analyze the effects of inhibition of P13k on IGF-1-induced plasmalemmal expansion and potential other growth cone responses. These studies will provide important new information on growth-regulatory events at the growth cone. The new knowledge is expected to enhance our understanding of neuronal network formation in the developing brain and may be applicable to the design of new strategies to enhance nerve regeneration after injury.

描述（由申请人提供） 轴突生长锥包含具有免疫化学的异常IGF-1受体 独特的B亚基，BGC。我们已经证明BDNF调节远端 BGC在海马神经元中的插入（在轴突生长锥上）。我们建议 反过来，IGF-1调节质膜膨胀，从而调节神经突的生长 通过控制血浆前体囊泡的胞吐插入 （PPV）。我们进一步假设至少有三种类型的PPV 可以差异插入，并且磷脂酰肌醇3-激酶（PI3K） 参与PPV插入的调节。 我们建议：（i）在测试管中研究生长锥的膜扩张 使用光学显微镜 战略; （ii）表征不同PPV类的属性 通过免疫分散； （iii）分析抑制p13k对 IGF-1诱导的浆膜扩张和潜在的其他生长锥反应。 这些研究将提供有关增长调节的重要新信息 生长锥的事件。新知识有望增强我们的 了解发育中的大脑中神经元网络形成，可能是 适用于设计新策略以增强神经再生的设计 受伤。