RT Journal Article SR Electronic T1 Localized Activation of p21-Activated Kinase Controls Neuronal Polarity and Morphology JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 8604 OP 8615 DO 10.1523/JNEUROSCI.0765-07.2007 VO 27 IS 32 A1 Jacobs, Tom A1 Causeret, Frédéric A1 Nishimura, Yoshiaki V. A1 Terao, Mami A1 Norman, Adele A1 Hoshino, Mikio A1 Nikolić, Margareta YR 2007 UL http://www.jneurosci.org/content/27/32/8604.abstract AB 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.