Role of IGF-1 receptor in axonal growth

描述(由申请人提供) 轴突生长锥体含有一种不寻常的IGF-1受体，免疫化学显示 独特的B亚基，BGC。我们已经证明了BDNF调节远端 BGC在海马神经元的插入(在轴突生长锥)。我们建议 反过来，IGF-1调节质膜扩张，从而调节轴突生长 通过控制质膜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 可以有差异地插入，并且磷脂酰肌醇3-激酶(PI3K) 参与了PPV插入的调节。 我们建议：(I)研究我们试管中生长锥处的膜膨胀。 用光学显微镜对培养中的完整生长锥进行了测定 策略；(2)表征分离的不同PPV类别的性质 通过免疫分离；以及(Iii)分析抑制P13K的作用。 IGF-1诱导的质膜扩张和潜在的其他生长锥反应。 这些研究将提供有关生长调节的重要新信息。 增长锥体上的事件。这一新知识有望增强我们的 了解发育中大脑中神经元网络的形成，并可能 适用于设计新的促进神经再生的策略 受伤。

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.