Caveolin Interacts with Trk A and p75NTR and Regulates Neurotrophin Signaling Pathways

Bilderback, Tim R.; Gazula, Valeswara‐Rao; Lisanti, Michael P.; Dobrowsky, Rick T.

doi:10.1074/jbc.274.1.257

Cited by 153 publications

(148 citation statements)

References 52 publications

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“…p75 NTR and TrkA are both significantly enriched in caveolae-like domains at the plasma membrane, and the two receptors may interact (at least functionally) within this micro-environment (44). Furthermore, indirect interaction between p75 NTR and TrkA via the mutually interacting protein caveolin-1 has been suggested (50).…”

Section: Structural Domains Of P75mentioning

confidence: 99%

The Extracellular Domain of p75NTR Is Necessary to Inhibit Neurotrophin-3 Signaling through TrkA

Mischel

Smith

Vining

et al. 2001

Journal of Biological Chemistry

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The TrkA receptor is activated primarily by nerve growth factor (NGF), but it can also be activated by high concentrations of neurotrophin 3 (NT-3). The pan-neurotrophin receptor p75 NTR NTR and TrkA could be coimmunoprecipitated from Xenopus oocytes. Our results suggest that the interaction of these two receptors on the cell surface mediated the inhibition of NT-3-activated signaling through TrkA.

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Section: Structural Domains Of P75mentioning

confidence: 99%

The Extracellular Domain of p75NTR Is Necessary to Inhibit Neurotrophin-3 Signaling through TrkA

Mischel

Smith

Vining

et al. 2001

Journal of Biological Chemistry

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“…Cav-1 and membrane/lipid rafts can regulate estrogen receptor signaling (58), glutamate receptor neurotransmission (9,43,59), and neurotrophin receptor signaling (TrkB and p75) (14,57). Although NMDAR subtypes are critical for neuroprotection against ischemic injury and for neurotransmission, their localization to extrasynaptic regions can facilitate neuronal cell death (33).…”

Section: Syncav1mentioning

confidence: 99%

Neuron-targeted Caveolin-1 Protein Enhances Signaling and Promotes Arborization of Primary Neurons

Head

Finley

et al. 2011

Journal of Biological Chemistry

113

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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 (TNF␣, IL-1␤) 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.Multiple signaling pathways have been identified that promote growth and survival of neurons and thereby facilitate the formation of synaptic connections that are essential for learning, memory, and the development of the CNS (1-3). Neurotransmitter and neurotrophic receptors, non-receptor tyrosine kinases, and other signaling mediators aggregate to mold and shape postsynaptic densities to permit high-fidelity signal transduction and the regulation of neuronal function (4 -6). A major non-protein component of synapses is cholesterol, which can be a limiting factor in synapse development, synaptic activity, and transmitter release (7).Increasing evidence shows that membrane/lipid rafts, discrete regions of the plasma membrane enriched in cholesterol, glycosphingolipids, and sphingomyelin organize prosurvival and progrowth neuronal signaling pathways (8 -10), regulate cAMP formation (11), and are essential for synapse development, stabilization, and maintenance (7, 12). Caveolin (Cav), 2 a cholesterol binding protein and scaffolding protein found within membrane/lipid rafts (13), organizes and targets certain neuronal growth-promoting proteins, such as components of the neurotransmitter and neurotrophic receptor signaling pathways, to membrane/lipid rafts. These include NMDA receptors, AMPA receptors, Trk receptors, GPC receptors, and Src family kinases (9, 14 -16). These receptors and signaling molecules can enhance cAMP formation, an essential second messenger for promoting neuronal growth and dendritic arborization (17-21), and are found within membrane/lipid rafts in growth cones (6). In the setting of traumatic brain injury and neurodegenerative disorders, interventions that activate signaling pathways to stimulate cAMP production thus have the potential to improve...

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“…p75 seems to interact with caveolin. Caveolae are presumably the site of neurotrophin-induced sphingomyelin hydrolysis (Bilderback et al 1997(Bilderback et al , 1999. Ceramide production is known to follow TNF binding to its receptor and to lead to NF-B activation (Wiegmann et al 1994).…”

Section: Signal Transduction Through the Neurotrophin Receptor P75mentioning

confidence: 99%

Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system

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2000

Genes Dev.

967

702

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Caveolin Interacts with Trk A and p75NTR and Regulates Neurotrophin Signaling Pathways

Cited by 153 publications

References 52 publications

The Extracellular Domain of p75NTR Is Necessary to Inhibit Neurotrophin-3 Signaling through TrkA

The Extracellular Domain of p75NTR Is Necessary to Inhibit Neurotrophin-3 Signaling through TrkA

Neuron-targeted Caveolin-1 Protein Enhances Signaling and Promotes Arborization of Primary Neurons

Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system

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