title: Calcineurin-dependent cofilin activation and increased retrograde actin flow drive 5-HT-dependent neurite outgrowth in Aplysia bag cell neurons.
abstract: Neurite outgrowth in response to soluble growth factors often involves changes in intracellular Ca(2+); however, mechanistic roles for Ca(2+) in controlling the underlying dynamic cytoskeletal processes have remained enigmatic. Bag cell neurons exposed to serotonin (5-hydroxytryptamine [5-HT]) respond with a threefold increase in neurite outgrowth rates. Outgrowth depends on phospholipase C (PLC) → inositol trisphosphate → Ca(2+) → calcineurin signaling and is accompanied by increased rates of retrograde actin network flow in the growth cone P domain. Calcineurin inhibitors had no effect on Ca(2+) release or basal levels of retrograde actin flow; however, they completely suppressed 5-HT-dependent outgrowth and F-actin flow acceleration. 5-HT treatments were accompanied by calcineurin-dependent increases in cofilin activity in the growth cone P domain. 5-HT effects were mimicked by direct activation of PLC, suggesting that increased actin network treadmilling may be a widespread mechanism for promoting neurite outgrowth in response to neurotrophic factors.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Zhang
authors.forename: Callen
authors.initials: C
authors.lastname: Hyland
authors.forename: David
authors.initials: D
authors.lastname: Van Goor
authors.forename: Paul
authors.initials: P
authors.lastname: Forscher
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001048:Aplysia; D001381:Azepines / Q000494:pharmacology; D015153:Blotting, Western; D019703:Calcineurin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D051338:Cofilin 1 / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence / Q000379:methods; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D000199:Actins; D001381:Azepines; D051338:Cofilin 1; D007295:Inositol Phosphates; D007797:Laminin; D009281:Naphthalenes; D017366:Serotonin Receptor Agonists; C070571:ML 7; D012701:Serotonin; D009219:Myosin-Light-Chain Kinase; D019703:Calcineurin; D010738:Type C Phospholipases; D002118:Calcium