title: Neuron-targeted caveolin-1 protein enhances signaling and promotes arborization of primary neurons.
abstract: 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.
authors.affiliation: Department of Anesthesiology, University of California, San Diego, La Jolla, California 92093, USA. bhead@ucsd.edu
authors.forename: Brian P
authors.initials: BP
authors.lastname: Head
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.forename: J Cameron
authors.initials: JC
authors.lastname: Finley
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Saldana
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Bonds
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyanohara
authors.forename: Ingrid R
authors.initials: IR
authors.lastname: Niesman
authors.forename: Sameh S
authors.initials: SS
authors.lastname: Ali
authors.forename: Fiona
authors.initials: F
authors.lastname: Murray
authors.forename: Paul A
authors.initials: PA
authors.lastname: Insel
authors.forename: David M
authors.initials: DM
authors.lastname: Roth
authors.forename: Hemal H
authors.initials: HH
authors.lastname: Patel
authors.forename: Piyush M
authors.initials: PM
authors.lastname: Patel
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018992:Myelin-Associated Glycoprotein / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009928:Organ Specificity / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D016704:Synapsins / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D016207:Cytokines; D018992:Myelin-Associated Glycoprotein; D016704:Synapsins; D002784:Cholesterol