The catalytic activity, but not receptor binding, of sPLA2s plays a critical role for neurite outgrowth induction in PC12 cells.
We previously showed that fungal secretory phospholipase A2 (sPLA2) induces neurite formation in PC12 cells in an L-type Ca2+ channel activity-dependent manner. In this study we compared neurite-inducing activity of different sPLA2s, including bee venom sPLA2 (bvPLA2), and found that it correlated with the ability of each sPLA2 to release fatty acids from live PC12 cells. Consistently, using several mutants of bvPLA2, we found that the enzymatic activity rather than the binding activity to the putative N-type receptor for neurotoxic sPLA2s 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.
Nakashima
Satoru
S
Department of Biotechnology, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657, Japan.
Kitamoto
Katsuhiko
K
Arioka
Manabu
M
D000818:Animals; D002384:Catalysis; D004789:Enzyme Activation / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism; D054501:Group II Phospholipases A2; D008024:Ligands; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D010741:Phospholipases A / Q000145:classification / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*
D005227:Fatty Acids; D008024:Ligands; D011956:Receptors, Cell Surface; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2