Nerve Growth Factor Enhances Tau Isoform Expression and Transcription in IMR32 Cells

Cheryl L Cragg,Bettina E Kalisch

doi:10.4236/nm.2014.52015

Abstract

The present study characterized the nerve growth factor (NGF)-mediated regulation of tau protein expression and transcription in IMR32 human neuroblastoma cells. Treatment of IMR32 cells with 50 ng/mL NGF resulted in increased levels of specific tau protein isoforms. A 550 bp fragment of the tau promoter was cloned and treatment of transfected IMR32 and PC12 cells with NGF also resulted in increased promoter activation, suggesting that the NGF-mediated increase in tau isoforms is regulated, at least in part, at the level of transcription. Pretreatment with the MAP kinase inhibitor U0126 or the PKC inhibitor bisindolylmaleimide 1 (BIS-1) attenuated the NGF-mediated increase in tau transcription, indicating that the NGF-mediated activation of the MAP kinase and PKC signaling pathways modulate tau transcription. Pre-treatment of cells with the Akt inhibitor, LY294002 or with NOS inhibitors Nω-nitro-L-arginine methylester (L-NAME) or s-methylisothiourea (S-MIU) had no effect on the NGF-mediated increase in tau promoter activation, suggesting that NO and the NGF-Akt signaling pathway do not modulate tau transcription. Taken together, these data demonstrate that NGF increases the levels of multiple human tau isoforms in IMR32 cells which may result, at least in part, from NGF-mediated PKC and MAP kinase-induced tau transcription.

Highlights

The microtubule associated protein tau is found predominately in the axons of neurons and functions in microtubule assembly and stabilization, enabling axonal transport of cellular components back and forth from the cellHow to cite this paper: Cragg, C.L. and Kalisch, B.E. (2014) Nerve Growth Factor Enhances Tau Isoform Expression and Transcription in IMR32 Cells
The other isoforms, in order from smallest to largest molecular weight, 0N4R, 1N3R, 1N4R, 2N3R, 2N4R appear above this band on the tau protein ladder and most were detected in the IMR32 cell lysates
The 2N3R isoform was only detected in extracts obtained from IMR32 cells treated with nerve growth factor (NGF), indicating the expression of this isoform increased following NGF treatment, this isoform was not detected consistently in all samples or on all blots and was not quantified

Summary

Introduction

The microtubule associated protein tau is found predominately in the axons of neurons and functions in microtubule assembly and stabilization, enabling axonal transport of cellular components back and forth from the cellHow to cite this paper: Cragg, C.L. and Kalisch, B.E. (2014) Nerve Growth Factor Enhances Tau Isoform Expression and Transcription in IMR32 Cells. The microtubule associated protein tau is found predominately in the axons of neurons and functions in microtubule assembly and stabilization, enabling axonal transport of cellular components back and forth from the cell. How to cite this paper: Cragg, C.L. and Kalisch, B.E. (2014) Nerve Growth Factor Enhances Tau Isoform Expression and Transcription in IMR32 Cells. E. Kalisch body to the synapse [1]-[4]. Overexpression of tau protein impairs anterograde axonal transport of cellular components required for axon and synaptic maintenance [5] and hyperphosphorylation of tau results in the formation of paired helical filaments which aggregate to form neurofibrillary tangles that impair neuronal functioning and contribute to cell death [6]-[12]

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