Neuron-targeted caveolin-1 protein enhances signaling and promotes arborization of primary neurons |
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Authors: | Head Brian P Hu Yue Finley J Cameron Saldana Michelle D Bonds Jacqueline A Miyanohara Atsushi Niesman Ingrid R Ali Sameh S Murray Fiona Insel Paul A Roth David M Patel Hemal H Patel Piyush M |
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Affiliation: | Department of Anesthesiology, University of California, San Diego, La Jolla, California 92093, USA. bhead@ucsd.edu |
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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. |
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Keywords: | Caveolin Membrane/Lipid Rafts Neuronal Signaling Dendritic Arborization |
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