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Publication : Localized activation of p21-activated kinase controls neuronal polarity and morphology.

First Author  Jacobs T Year  2007
Journal  J Neurosci Volume  27
Issue  32 Pages  8604-15
PubMed ID  17687038 Mgi Jnum  J:123684
Mgi Id  MGI:3719292 Doi  10.1523/JNEUROSCI.0765-07.2007
Citation  Jacobs T, et al. (2007) Localized activation of p21-activated kinase controls neuronal polarity and morphology. J Neurosci 27(32):8604-15
abstractText  In the developing forebrain, neuronal polarization is a stepwise and initially reversible process that underlies correct migration and axon specification. Many aspects of cytoskeletal changes that accompany polarization are currently molecularly undefined and thus poorly understood. Here we reveal that the p21-activated kinase (Pak1) is essential for the specification of an axon and dendrites. In hippocampal neurons, activation of Pak1 is spatially restricted to the immature axon despite its uniform presence in all neurites. Hyperactivation of Pak1 at the membrane of all neurites or loss of Pak1 expression disrupts both neuronal morphology and the distinction between an axon and dendrites. We reveal that Pak1 acts on polarity in a kinase-dependent manner, by affecting the F-actin and microtubule cytoskeleton at least in part through Rac1 and cofilin. Our data are the first to demonstrate the importance of localized Pak1 kinase activation for neuronal polarization and differentiation.
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