TY - JOUR
T1 - Regulation of low affinity neurotrophin receptor (p75NTR) by early growth response (Egr) transcriptional regulators
AU - Gao, Xiaoguang
AU - Daugherty, Rebecca L.
AU - Tourtellotte, Warren G.
N1 - Funding Information:
We thank L. Eldredge and J. Carter for helpful discussion and comments on the manuscript. This study was supported by The National Institutes of Health (NS046468 and NS040748).
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/12
Y1 - 2007/12
N2 - The low affinity neurotrophin receptor p75NTR is a multifunctional receptor with important roles in neurotrophin signaling, axon outgrowth, and oligodendroglia and neuron survival. It is transcriptionally regulated with spatial and temporal precision during nervous system development, injury and regeneration. Very little is known about how p75NTR expression is dynamically regulated but it is likely to influence how p75NTR signals in particular cellular contexts. Here, we identify the early growth response (Egr) transcriptional regulators, Egr1 and Egr3, as direct modulators of p75NTR gene expression. Egr1 and Egr3 bind and transactivate the p75NTR promoter in vitro and in vivo, using distinct response elements on the p75NTR promoter. Consistent with these results, p75NTR expression is greatly diminished in muscle spindle stretch receptors and in peripheral nerve Schwann cells in Egr gene deficient mice. Taken together, the results elucidate a novel mechanism whereby Egr proteins can directly modulate p75NTR expression and signaling in vivo.
AB - The low affinity neurotrophin receptor p75NTR is a multifunctional receptor with important roles in neurotrophin signaling, axon outgrowth, and oligodendroglia and neuron survival. It is transcriptionally regulated with spatial and temporal precision during nervous system development, injury and regeneration. Very little is known about how p75NTR expression is dynamically regulated but it is likely to influence how p75NTR signals in particular cellular contexts. Here, we identify the early growth response (Egr) transcriptional regulators, Egr1 and Egr3, as direct modulators of p75NTR gene expression. Egr1 and Egr3 bind and transactivate the p75NTR promoter in vitro and in vivo, using distinct response elements on the p75NTR promoter. Consistent with these results, p75NTR expression is greatly diminished in muscle spindle stretch receptors and in peripheral nerve Schwann cells in Egr gene deficient mice. Taken together, the results elucidate a novel mechanism whereby Egr proteins can directly modulate p75NTR expression and signaling in vivo.
KW - Development
KW - Egr
KW - Low affinity neurotrophin receptor
KW - Transcriptional regulation
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U2 - 10.1016/j.mcn.2007.08.013
DO - 10.1016/j.mcn.2007.08.013
M3 - Article
C2 - 17916431
AN - SCOPUS:35448933117
VL - 36
SP - 501
EP - 514
JO - Molecular and Cellular Neurosciences
JF - Molecular and Cellular Neurosciences
SN - 1044-7431
IS - 4
ER -