A role for the cytoskeleton-associated protein palladin in neurite outgrowth

The outgrowth of neurites is a critical step in neuronal maturation, and it is well established that the actin cytoskeleton is involved in this proces s. Investigators from our laboratory recently described a novel protein nam ed palladin, which has been shown to play an essential role in organizing t he actin cytoskeleton in cultured fibroblasts. We investigated the expressi on of palladin in the developing rat brain by Western blot and found that t he E18 brain contained a unique variant of palladin that is significantly s maller (similar to 85 kDa) than the common form found in other developing t issues (90-92 kDa). Because the expression of a tissue-specific isoform sug gests the possibility of a cell type-specific function, we investigated the localization and function of palladin in cultured cortical neurons. Pallad in was found preferentially targeted to the developing axon but not the den drites and was strongly localized to the axonal growth cone. When palladin expression was attenuated by transfection with antisense constructs in both the B35 neuroblastoma cell line and in primary cortical neurons, a reducti on in the expression of palladin resulted in a failure of neurite outgrowth . These results implicate palladin as a critical component of the developin g nervous system, with an important role in axonal extension.