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

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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.