scholarly journals Ligand-Dependent Cleavage of the P75 Neurotrophin Receptor Is Necessary for NRIF Nuclear Translocation and Apoptosis in Sympathetic Neurons

Neuron ◽  
2006 ◽  
Vol 50 (2) ◽  
pp. 219-232 ◽  
Author(s):  
Rajappa S. Kenchappa ◽  
Niccolò Zampieri ◽  
Moses V. Chao ◽  
Philip A. Barker ◽  
Henry K. Teng ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Sympathetic Neurons ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor

scholarly journals The p75 Neurotrophin Receptor Mediates Neuronal Apoptosis and Is Essential for Naturally Occurring Sympathetic Neuron Death

1998 ◽  
Vol 140 (4) ◽  
pp. 911-923 ◽  
Author(s):  
Shernaz X. Bamji ◽  
Marta Majdan ◽  
Christine D. Pozniak ◽  
Daniel J. Belliveau ◽  
Raquel Aloyz ◽  
...  
Keyword(s):  
Neuronal Apoptosis ◽  
Sympathetic Neurons ◽  
Sympathetic Neuron ◽  
Neurotrophin Receptor ◽  
Tyrosine Kinase Receptor ◽  
P75 Neurotrophin Receptor ◽  
Neuron Death ◽  
Naturally Occurring ◽  
Physiological Relevance ◽  
Normal Period

Abstract. To determine whether the p75 neurotrophin receptor (p75NTR) plays a role in naturally occurring neuronal death, we examined neonatal sympathetic neurons that express both the TrkA tyrosine kinase receptor and p75NTR. When sympathetic neuron survival is maintained with low quantities of NGF or KCl, the neurotrophin brain-derived neurotrophic factor (BDNF), which does not activate Trk receptors on sympathetic neurons, causes neuronal apoptosis and increased phosphorylation of c-jun. Function-blocking antibody studies indicate that this apoptosis is due to BDNF-mediated activation of p75NTR. To determine the physiological relevance of these culture findings, we examined sympathetic neurons in BDNF−/− and p75NTR−/− mice. In BDNF−/− mice, sympathetic neuron number is increased relative to BDNF+/+ littermates, and in p75NTR−/− mice, the normal period of sympathetic neuron death does not occur, with neuronal attrition occurring later in life. This deficit in apoptosis is intrinsic to sympathetic neurons, since cultured p75NTR−/− neurons die more slowly than do their wild-type counterparts. Together, these data indicate that p75NTR can signal to mediate apoptosis, and that this mechanism is essential for naturally occurring sympathetic neuron death.

The p75 neurotrophin receptor influences NT-3 responsiveness of sympathetic neurons in vivo

10.1038/11158 ◽  
1999 ◽  
Vol 2 (8) ◽  
pp. 699-705 ◽  
Author(s):  
Christine Brennan ◽  
Kimberly Rivas-Plata ◽  
Story C. Landis
Keyword(s):  
Sympathetic Neurons ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor

scholarly journals Heterogeneous ventricular sympathetic innervation, altered β-adrenergic receptor expression, and rhythm instability in mice lacking the p75 neurotrophin receptor

2010 ◽  
Vol 298 (6) ◽  
pp. H1652-H1660 ◽  
Author(s):  
Christina U. Lorentz ◽  
Eric N. Alston ◽  
Todd Belcik ◽  
Jonathan R. Lindner ◽  
George D. Giraud ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Sympathetic Neurons ◽  
Sympathetic Innervation ◽  
Sympathetic Nerves ◽  
Nerve Fibers ◽  
Receptor Expression ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Semaphorin 3A

Sympathetic nerves stimulate cardiac function through the release of norepinephrine and the activation of cardiac β1-adrenergic receptors. The sympathetic innervation of the heart is sculpted during development by chemoattractive factors including nerve growth factor (NGF) and the chemorepulsive factor semaphorin 3a. NGF acts through the TrkA receptor and the p75 neurotrophin receptor (p75NTR) in sympathetic neurons. NGF stimulates sympathetic axon extension into the heart through TrkA, but p75NTR modulates multiple coreceptors that can either stimulate or inhibit axon outgrowth. In mice lacking p75NTR, the sympathetic innervation density in target tissues ranges from denervation to hyperinnervation. Recent studies have revealed significant changes in the sympathetic innervation density of p75NTR-deficient (p75NTR−/−) atria between early postnatal development and adulthood. We examined the innervation of adult p75NTR−/− ventricles and discovered that the subendocardium of the p75NTR−/− left ventricle was essentially devoid of sympathetic nerve fibers, whereas the innervation density of the subepicardium was normal. This phenotype is similar to that seen in mice overexpressing semaphorin 3a, and we found that sympathetic axons lacking p75NTR are more sensitive to semaphorin 3a in vitro than control neurons. The lack of subendocardial innervation was associated with decreased dP/d t, altered cardiac β1-adrenergic receptor expression and sensitivity, and a significant increase in spontaneous ventricular arrhythmias. The lack of p75NTR also resulted in increased tyrosine hydroxylase content in cardiac sympathetic neurons and elevated norepinephrine in the right ventricle, where innervation density was normal.

Estrogen alters trkA and p75 neurotrophin receptor expression within sympathetic neurons

2005 ◽  
Vol 65 (2) ◽  
pp. 192-204 ◽  
Author(s):  
Wohaib Hasan ◽  
H. Jesse Smith ◽  
Alison Y. Ting ◽  
Peter G. Smith
Keyword(s):  
Sympathetic Neurons ◽  
Receptor Expression ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor

scholarly journals c-jun is essential for sympathetic neuronal death induced by NGF withdrawal but not by p75 activation

2002 ◽  
Vol 158 (3) ◽  
pp. 453-461 ◽  
Author(s):  
M. Palmada ◽  
S. Kanwal ◽  
N.J. Rutkoski ◽  
C. Gustafson-Brown ◽  
R.S. Johnson ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Sympathetic Neurons ◽  
Neurotrophin Receptor ◽  
Null Mutation ◽  
P75 Neurotrophin Receptor ◽  
Vertebrate Development ◽  
Apoptotic Response ◽  
Dapi Staining ◽  
Embryonic Lethal ◽  
Factor C

Sympathetic neurons depend on NGF binding to TrkA for their survival during vertebrate development. NGF deprivation initiates a transcription-dependent apoptotic response, which is suggested to require activation of the transcription factor c-Jun. Similarly, apoptosis can also be induced by selective activation of the p75 neurotrophin receptor. The transcriptional dependency of p75-mediated cell death has not been determined; however, c-Jun NH2-terminal kinase has been implicated as an essential component. Because the c-jun–null mutation is early embryonic lethal, thereby hindering a genetic analysis, we used the Cre-lox system to conditionally delete this gene. Sympathetic neurons isolated from postnatal day 1 c-jun–floxed mice were infected with an adenovirus expressing Cre recombinase or GFP and analyzed for their dependence on NGF for survival. Cre immunopositive neurons survived NGF withdrawal, whereas those expressing GFP or those uninfected underwent apoptosis within 48 h, as determined by DAPI staining. In contrast, brain-derived neurotrophic factor (BDNF) binding to p75 resulted in an equivalent level of apoptosis in neurons expressing Cre, GFP, and uninfected cells. Nevertheless, cycloheximide treatment prevented BDNF-mediated apoptosis. These results indicate that whereas c-jun is required for apoptosis in sympathetic neurons on NGF withdrawal, an alternate signaling pathway must be induced on p75 activation.

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