Role of IGF-1 receptor in axonal growth

描述（由申请人提供） 轴突生长锥含有一种不寻常的IGF-1受体， 不同的B亚基，Bgc。我们已经证明，BDNF调节远端的 Bgc在海马神经元中的插入（在轴突生长锥处）。我们提出 进而IGF-1调节质膜扩张，进而调节神经突生长 通过控制质膜前体小泡的胞吐插入 （PPV）。我们进一步假设至少有三种类型的PPV， 可能插入差异，磷脂酰肌醇3-激酶（PI 3 k） 参与PPV插入的调节。 我们建议：（i）在我们的试管中研究生长锥处的膜扩张 测定，以及使用光学显微镜在培养物中的完整生长锥中 策略;（ii）表征不同PPV类分离的属性 通过免疫隔离;和（iii）分析抑制P13 k对 IGF-1诱导的质膜扩张和潜在的其他生长锥反应。 这些研究将为生长调节提供重要的新信息。 生长锥上的事件。新知识有望提高我们的 了解发育中的大脑神经元网络的形成， 适用于设计新的策略，以增强神经再生后， 损伤

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.