Neuron-targeted caveolin-1 protein enhances signaling and promotes arborization of primary neurons

J Biol Chem. 2011 Sep 23;286(38):33310-21. doi: 10.1074/jbc.M111.255976. Epub 2011 Jul 28.


Decreased expression of prosurvival and progrowth-stimulatory pathways, in addition to an environment that inhibits neuronal growth, contribute to the limited regenerative capacity in the central nervous system following injury or neurodegeneration. Membrane/lipid rafts, plasmalemmal microdomains enriched in cholesterol, sphingolipids, and the protein caveolin (Cav) are essential for synaptic development/stabilization and neuronal signaling. Cav-1 concentrates glutamate and neurotrophin receptors and prosurvival kinases and regulates cAMP formation. Here, we show that primary neurons that express a synapsin-driven Cav-1 vector (SynCav1) have increased raft formation, neurotransmitter and neurotrophin receptor expression, NMDA- and BDNF-mediated prosurvival kinase activation, agonist-stimulated cAMP formation, and dendritic growth. Moreover, expression of SynCav1 in Cav-1 KO neurons restores NMDA- and BDNF-mediated signaling and enhances dendritic growth. The enhanced dendritic growth occurred even in the presence of inhibitory cytokines (TNFα, IL-1β) and myelin-associated glycoproteins (MAG, Nogo). Targeting of Cav-1 to neurons thus enhances prosurvival and progrowth signaling and may be a novel means to repair the injured and neurodegenerative brain.

Publication types

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

MeSH terms

  • Animals
  • Axons / drug effects
  • Axons / metabolism
  • Caveolin 1 / metabolism*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cholesterol / metabolism
  • Cytokines / pharmacology
  • Dendrites / drug effects
  • Dendrites / metabolism
  • Membrane Microdomains / drug effects
  • Membrane Microdomains / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myelin-Associated Glycoprotein / pharmacology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Organ Specificity / drug effects
  • Signal Transduction* / drug effects
  • Synapsins / metabolism


  • Caveolin 1
  • Cytokines
  • Myelin-Associated Glycoprotein
  • Synapsins
  • Cholesterol