Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse

Semaphorin 3A is a chemorepulsive axonal guidance molecule that depolymeriz es the actin cytoskeleton and collapses growth cones of dorsal root ganglia neurons. Here we investigate! the role of LIM-kinase 1, which phosphorylat es an actin-depolymerizimg protein, cofilin, in semaphorin 3A-induced growt h cone collapse. Semaphorin 3A induced phosphorylation and dephosphorylatio n of cofilin at growth cones sequentially. A synthetic cell-permeable pepti de containing a cofilin phosphorylation site inhibited LIM-kinase in vitro and in vivo, and essentially suppressed semaphorin 3A-induced growth cone c ollapse. A dominant-negative LIM kinase, which could not be activated by PA K or ROCK, suppressed the collapsing activity of semaphorin 3A. Phosphoryla tion of cofilin by LIM-kinase may be a critical signaling event in growth c one collapse by semaphorin 3A.