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Wnt signaling in neuron polarity

By M. Nellestijn


Several lines of evidence suggest that Wnt signaling is involved in the establishment of neuronal polarity. Wnt proteins are a group of glycoproteins which play an important role in development and disease. A key role player in this pathway is GSK3. GSK3 is able to phosphorylate a broad range of microtubule-binding proteins (MBPs), which are involved in neuronal polarity by regulating microtubule dynamics. Among these proteins are microtubule associated protein 1B (MAP1B), collapsing response mediator protein 2 (CRMP2) and adenomatous polyposis coli (APC). Microtubule binding proteins are able to stabilize microtubules, which is required for the outgrowth of an axon. In the process, called neuronal polarization, one axon and several smaller dendrites are formed. In vivo axons and dendrites grow in a preferred direction. GSK3 is able to phosphorylate microtubule binding proteins, resulting in unstable microtubules. Stabilization of the dendrite is necessary in the neurite that will become the axon. In this thesis I will discuss how neuronal polarization and polarity is influenced by Wnt pathway components and specifically GSK3. The important role of GSK3 in neuronal development is consistent with the finding that GSK3 is implicated in neuronal disorders and neurodegenerative diseases. Manipulation of GSK3 and its regulation by the Wnt pathway may therefore contribute to the development of new therapies

Topics: Wnt signaling, GSK3, Microtubules, Neuronal polarity
Year: 2012
OAI identifier: oai:dspace.library.uu.nl:1874/254235
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