Overexpression of Nogo-A changes nerve growth factor signaling dynamics in PC12 cells

被引:0
作者
Farrer, Robert G. [1 ]
Kartje, Gwendolyn L. [1 ,2 ]
机构
[1] Edward Hines Jr VA Hosp, RES SERV, HINES, IL USA
[2] Loyola Univ Chicago, Hlth Sci Div, Dept Mol Pharmacol & Neurosci, Maywood, IL USA
基金
美国国家卫生研究院;
关键词
Calcium; Calmodulin; Extracellular signal-regulated kinase 1/2; (Erk1/2); Nogo-A; TrkA; p75 neurotrophin receptor (p75NTR); KINASE PATHWAY; RECEPTOR; TRKA; EXPRESSION; ACTIVATION; PROTEIN; REGENERATION; TRANSIENT; OUTGROWTH; P75(NTR);
D O I
10.1016/j.cellsig.2024.111569
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The nerve growth factor (NGF) receptor TrkA is a tightly regulated receptor tyrosine kinase that activates neuronal signaling pathways promoting cell survival in addition to axonal and dendritic outgrowth. Previously, we showed that NGF and TrkA signaling is altered in neuron-like PC12 cells that overexpress Nogo-A, a protein known to influence axonal outgrowth and dendritic arborization associated with neuronal plasticity. In the present report, we provide evidence for changes in NGF-mediated receptor-level and downstream signaling that occur in cells overexpressing Nogo-A. NGF stimulation increased the association of Nogo-A with TrkA, which corresponded to a decrease in sustained phosphorylation of TrkA and its downstream effectors Erk1/2, indicating that Nogo-A plays a role in the temporal regulation of this pathway. Furthermore, co-immunoprecipitation of the p75 neurotrophin receptor (p75NTR) with TrkA was significantly reduced in cells overexpressing Nogo-A, suggesting that Nogo-A blocked this interaction. Analysis of calcium and calmodulin involvement in NGF-induced activation of Erk1/2 revealed a calcium and calmodulin-dependent inhibition of sustained phosphorylation in Nogo-A-overexpressing cells but not in wild type cells, suggesting that Nogo-A facilitated the activation of calcium/calmodulin to alter NGF signaling. Taken together, these results provide evidence for Nogo-A regulation of NGF signaling, in part by modifying calcium and calmodulin-dependent mechanisms.
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页数:8
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