Group IVA phospholipase A₂ is necessary for growth cone repulsion and collapse.
The repellent semaphorin 3A (Sema3A) causes growth cone turning or collapse by triggering cytoskeletal rearrangements and detachment of adhesion sites. Growth cone detachment is dependent on eicosanoid activation of protein kinase C epsilon (PKCε), but the characterization of the phospholipase A(2) (PLA(2) ) that releases arachidonic acid (AA) for eicosanoid synthesis has remained elusive. Here, we show, in rat dorsal root ganglion (DRG) neurons, that Sema3A stimulates PLA(2) activity, that Sema3A-induced growth cone turning and collapse are dependent on the release of AA, and that the primary PLA(2) involved is the group IV α isoform (GIVA). Silencing GIVA expression renders growth cones resistant to Sema3A-induced collapse, and GIVA inhibition reverses Sema3A-induced repulsion into attraction. These studies identify a novel, early step in Sema3A-signaling and a PLA(2) necessary for growth cone repulsion and collapse.
Department of Pediatrics, Neuroscience Program, and Colorado Intellectual and Developmental Disabilities Research Center, University of Colorado School of Medicine, Aurora, Colorado, USA.
Staci D
SD
Sanford
Bo Goen
BG
Yun
Christina C
CC
Leslie
Robert C
RC
Murphy
Karl H
KH
Pfenninger
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D015870:Gene Expression / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D054513:Group IV Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D040121:Semaphorin-3A / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014162:Transfection
D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D040121:Semaphorin-3A; D049452:Green Fluorescent Proteins; D011493:Protein Kinase C; D054513:Group IV Phospholipases A2