Pak1 Regulates Dendritic Branching and Spine Formation

ABSTRACT: The serine/threonine kinase p21-acti-vated kinase 1 (Pak1) modulates actin and microtubule dynamics. The neuronal functions of Pak1, despite its abundant expression in the brain, have not yet been fully delineated. Previously, we reported that Pak1 mediates initiation of dendrite formation. In the present study, the role of Pak1 in dendritogenesis, spine forma-tion and maintenance was examined in detail. Overex-pression of constitutively active-Pak1 in immature corti-cal neurons increased not only the number of the pri-mary branching on apical dendrites but also the number of basal dendrites. In contrast, introduction of dominant negative-Pak caused a reduction in both of these mor-phological features. The length and the number of sec-ondary apical branch points of dendrites were not sig-nificantly different in cultured neurons expressing these mutant forms, suggesting that Pak1 plays a role in den-dritogenesis. Pak1 also plays a role in the formation and maintenance of spines, as evidenced by the altered spine morphology, resulting from overexpression of mutant forms of Pak1 in immature and mature hippocampal neurons. Thus, our results provide further evidence of the key role of Pak1 in the regulation of dendritogenesis, dendritic arborization, the spine formation, and main