PDLIM5 mediates PKCε translocation in PMA-induced growth cone collapse

Growth cone collapse is a critical repulsive response to various guidance cues for axon guidance. Protein kinase C epsilon (PKC epsilon) plays important regulation roles in such responses. Translocation of PKC epsilon from cytoplasm to membrane is crucial to archive its regulatory roles in this process. We previously reported that PDLIM5 could selectively recruit PKC epsilon to its specific substrate in neurons. However, the molecular mechanism of PKC epsilon translocation in the neuronal growth cone collapse remains elusive. Here, we demonstrated that PDLIM5 and PKC epsilon co-existed in the nerve growth cones. By interacting with alpha-actinin, but not beta-actin or beta-tubulin, PDLIM5 might contribute to regulation of remodeling of the microfilaments in neurons. Meanwhile, PDLIM5 could also bind to PKC epsilon to form PDLIM5-PKC epsilon complexes in growth cones. In the primary cultured neurons, activation of PKC epsilon by PMA resulted in translocation of both PKC epsilon and PDLIM5 from cytoplasm to the membrane. Knockdown of either PDLIM5 or PKC epsilon rescued the neuron from PMA-induced growth cone collapse. Furthermore, in neurons, application of PDLIM5 shRNA or over-expression of PDLIM5 LIM1-3 mutants reduced the amount of PKC epsilon in the membrane. Together, these results suggest that PDLIM5 acts as a scaffold protein by mediated PKC epsilon translocated to the membrane in PMA-induced growth cone collapse. (C) 2014 Elsevier Inc. All rights reserved.