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Neuron‐targeted caveolin‐1 enhances pro‐survival signaling, dendritic growth and axonal sprouting
Author(s) -
Head Brian Patrick,
Hu Yue,
Roth David M.,
Patel Hemal H.,
Patel Piyush M.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.651.5
Membrane/lipid rafts (MLR), are plasmalemmal microdomains enriched in sphingolipids, cholesterol, and the protein caveolin (Cav) and are essential for neuronal signaling and synaptic development/stabilization. Cav‐1 organizes glutamate and neurotrophin receptors (e.g. NMDAR, AMPAR, GPCRs, Trk), pro‐survival kinases, and regulates cAMP formation. We hypothesized that neuron‐targeted Cav‐1 initiates MLR formation and enhances pro‐survival signaling pathways, thereby promoting neuronal survival, dendritic growth, and axonal sprouting. Primary neurons in vitro (DIV4) were transfected with a viral vector encoding a synapsin promoter upstream of Cav‐1 cDNA ( SynCav1 ). SynCav1 significantly enhanced MLR (CT‐B), PSD‐95, NR2A, NR2B, AMPAR, and TrkB expression, BDNF‐mediated activation of P‐TrkB, P‐Akt, and P‐ERK1/2, NMDA‐mediated activation of P‐Src, P‐CaMKII, and P‐ERK1/2, and agonist stimulated cAMP formation 3 days post tranfection. Confocal microscopy showed a 4‐fold increase in dendritic (b 3 ‐tubulin) and axonal (galectin‐1a, GAP43) growth (21 d post). Re‐expression of Cav‐1 in Cav‐1 KO neurons restored NMDA and BDNF‐mediated pro‐survival signaling (3 d) and enhanced axonal growth (21 d). In essence, neuron‐targeted Cav‐1 leads to enhanced pro‐survival and pro‐growth signaling pathways and could potentially lead to neuronal regeneration in the neurodegenerative and injured brain.