Calcineurin-dependent cofilin activation and increased retrograde actin flow drive 5-HT-dependent neurite outgrowth in Aplysia bag cell neurons

Mol Biol Cell. 2012 Dec;23(24):4833-48. doi: 10.1091/mbc.E12-10-0715. Epub 2012 Oct 24.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • Aplysia
  • Azepines / pharmacology
  • Blotting, Western
  • Calcineurin / metabolism*
  • Calcium / metabolism
  • Cells, Cultured
  • Cofilin 1 / metabolism*
  • Inositol Phosphates / metabolism
  • Laminin / metabolism
  • Microscopy, Confocal
  • Microscopy, Fluorescence / methods
  • Myosin-Light-Chain Kinase / antagonists & inhibitors
  • Myosin-Light-Chain Kinase / metabolism
  • Naphthalenes / pharmacology
  • Neurites / drug effects*
  • Neurites / metabolism
  • Neurites / physiology
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Serotonin / pharmacology*
  • Serotonin Receptor Agonists / pharmacology
  • Signal Transduction / drug effects
  • Type C Phospholipases / metabolism

Substances

  • Actins
  • Azepines
  • Cofilin 1
  • Inositol Phosphates
  • Laminin
  • Naphthalenes
  • Serotonin Receptor Agonists
  • ML 7
  • Serotonin
  • Myosin-Light-Chain Kinase
  • Calcineurin
  • Type C Phospholipases
  • Calcium