The role of GTPases and CRMP proteins in the establishment of neuronal polarity

极化形态的形成是神经元分化的重要一步。对模型系统的研究表明，内在或外在的不对称信号由小的GTP酶解释，这些小的GTP酶重塑皮质肌动蛋白细丝，作为建立细胞极性的关键步骤。这些局部的分子不对称性随后被依赖于微管的过程放大和传播。尽管所有现有的证据表明，该模型可能也适用于神经元极性的建立，但仍有待于证明GTP酶在神经元中发挥类似的作用。特别是，调节它们在建立分子不对称性中的功能和潜在的空间和时间调节的分子机制仍有待阐明。在拟议的项目中，我们计划研究GTP酶和CRMPs，一种微管结合蛋白家族，在培养的分离的海马神经元中的作用。这些蛋白质的过度表达突变对神经元的分子和形态分化的影响将被研究。此外，我们还将分析与这些蛋白质相互作用的因素，以了解调节它们功能的分子机制。

The development of a polarized morphology is an essential step in the differentiation of neurons. Studies of model systems have shown that intrinsic or extrinsic asymmetry cues are interpreted by small GTPases that remodel cortical actin filaments as an essential step in the establishment of cellular polarity. These localized molecular asymmetries are subsequently amplified and propagated by processes that depend on microtubules. Although all available evidence suggests that this model probably is also valid for the establishment of neuronal polarity it remains to be shown that GTPases perform similar roles in neurons. In particular, the molecular mechanisms mediating their function in the establishing molecular asymmetries and underlying their spatial and temporal regulation remain to be elucidated. In the proposed project we plan to study the role of GTPases and CRMPs, a family of microtubule-binding proteins, in cultured dissociated hippocampal neurons. The effects of overexpressing mutants of these proteins on the molecular and morphological differentiation of neurons will be studied. In addition, we will analyze factors interacting with these proteins to understand the molecular mechanisms mediating their function.