Inhibition of neurite extension by overexpression of individual domains of LIM kinase 1

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Abstract
Lin‐11, Isl‐1 and Mec‐3 (LIM) kinases are serine/threonine kinases that phosphorylate cofilin, an actin depolymerizing protein. LIM kinases have a highly modular structure composed of two N‐terminal LIM domains (LIM 1/2), a PSD‐95, Dlg and ZO‐1 (PDZ) domain and a C‐terminal protein kinase domain. Here, we overexpressed individual domains of mouse LIM kinase 1 (LIMK1) in PC12 cells and investigated their effects on neurite outgrowth. Although none of the LIMK1 domains had an effect on spontaneous neurite outgrowth, the N‐terminal LIM 1/2 domains strongly inhibited differentiation of PC12 cells after stimulation with both nerve growth factor (NGF) and the Rho‐kinase inhibitor Y‐27632. In contrast, the overexpressed PDZ domain reduced neurite outgrowth only when differentiation had been induced by Y‐27632, but not by NGF. Our data suggest that the different non‐catalytic N‐terminal domains of LIMK1 contribute to the regulation of neurite extension by using distinct signal transduction pathways.