The catalytic activity, but not receptor binding, of sPLA 2 s plays a critical role for neurite outgrowth induction in PC12 cells

We previously showed that fungal secretory phospholipase A 2 (sPLA 2 ) induces neurite formation in PC12 cells in an L-type Ca 2+ channel activity-dependent manner. In this study we compared neurite-inducing activity of different sPLA 2 s, including bee venom sPLA 2 (bvPLA 2 ), and found that it correlated with the ability of each sPLA 2 to release fatty acids from live PC12 cells. Consistently, using several mutants of bvPLA 2, we found that the enzymatic activity rather than the binding activity to the putative N-type receptor for neurotoxic sPLA 2 s is the critical determinant for the neuritogenic response. These results imply that the neurite outgrowth is elicited by the messenger(s) produced upon degradation of membrane phospholipids.