p75(NTR) expression and nuclear localization of p75(NTR) intracellular domain in spiral ganglion Schwann cells following deafness correlate with cell proliferation

Matthew J Provenzano; Sarah A Minner; Kaitlin Zander; J Jason Clark; Catherine J Kane; Steven H Green; Marlan R Hansen

doi:10.1016/j.mcn.2011.05.010

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p75(NTR) expression and nuclear localization of p75(NTR) intracellular domain in spiral ganglion Schwann cells following deafness correlate with cell proliferation

Journal article

Peer reviewed

p75(NTR) expression and nuclear localization of p75(NTR) intracellular domain in spiral ganglion Schwann cells following deafness correlate with cell proliferation

Matthew J Provenzano, Sarah A Minner, Kaitlin Zander, J Jason Clark, Catherine J Kane, Steven H Green and Marlan R Hansen

Molecular and cellular neurosciences, Vol.47(4), pp.306-315

08/2011

DOI: 10.1016/j.mcn.2011.05.010

PMCID: PMC3137691

PMID: 21658451

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Abstract

Spiral ganglion Schwann cells (SGSCs) myelinate spiral ganglion neurons (SGNs) and represent a potential source of neurotrophic support for SGNs. Deafening due to loss of hair cells results in gradual degeneration and death of SGNs. Successful efforts to maintain or regenerate a functional auditory nerve may depend on a healthy population of SGSCs, yet the responses of SGSCs to neural injury remain largely unknown. Here we investigate the role of p75(NTR) in SGSC responses to gradual denervation. Following deafening, SGSCs in the osseous spiral lamina (OSL) and, subsequently, in Rosenthal's canal (RC) expressed elevated p75(NTR) compared to hearing controls. p75(NTR)-positive cells co-labeled with S100 and RIP antibodies (Schwann cell markers), but not with anti-neurofilament. The pattern of p75(NTR) expression mirrored the pattern of neural degeneration, beginning in the OSL of the cochlea base and later extending into the apex. SGSCs expressed sortilin, a p75(NTR) co-receptor for pro-neurotrophins. Both pro-nerve growth factor (pro-NGF) and pro-brain derived neurotrophic factor (proBDNF) induced apoptosis in cultured SGSCs. Deafened animals exhibited significantly higher levels of SGSC proliferation (as measured by BrdU uptake) compared to hearing animals while total Schwann cell density remained stable, suggesting a tight regulation of SGSC proliferation and cell death. SGSCs undergoing cell division lose p75(NTR) expression from the cell surface and demonstrate nuclear localization of the intracellular domain (ICD), raising the possibility that p75(NTR) cleavage and ICD nuclear localization regulate SGSC proliferation. These results suggest that p75(NTR) contributes to SGSC responses to deafening and neural degeneration.

Cell Proliferation

Nerve Growth Factor - metabolism

Receptor, Nerve Growth Factor - genetics

Cells, Cultured

Rats

Deafness - physiopathology

Schwann Cells - metabolism

Spiral Ganglion - metabolism

Adaptor Proteins, Vesicular Transport - metabolism

Rats, Sprague-Dawley

Spiral Ganglion - cytology

Schwann Cells - cytology

Protein Precursors - metabolism

Deafness - pathology

Animals

Cell Nucleus - metabolism

Brain-Derived Neurotrophic Factor - metabolism

Receptor, Nerve Growth Factor - metabolism

Details

Title: Subtitle: p75(NTR) expression and nuclear localization of p75(NTR) intracellular domain in spiral ganglion Schwann cells following deafness correlate with cell proliferation
Creators: Matthew J Provenzano - Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA 52242-1078, USA
Sarah A Minner
Kaitlin Zander
J Jason Clark
Catherine J Kane
Steven H Green
Marlan R Hansen
Resource Type: Journal article
Publication Details: Molecular and cellular neurosciences, Vol.47(4), pp.306-315
DOI: 10.1016/j.mcn.2011.05.010
PMID: 21658451
PMCID: PMC3137691
NLM abbreviation: Mol Cell Neurosci
ISSN: 1044-7431
eISSN: 1095-9327
Publisher: United States
Grant note: R01DC002961 / NIDCD NIH HHS R01 DC009801-01A1 / NIDCD NIH HHS R01 DC009801 / NIDCD NIH HHS R01 DC002961-06 / NIDCD NIH HHS P30 DC010362 / NIDCD NIH HHS R01 DC002961 / NIDCD NIH HHS T32 DC000040 / NIDCD NIH HHS P30 DC010362-01A1 / NIDCD NIH HHS R01 DC009405 / NIDCD NIH HHS
Language: English
Date published: 08/2011
Academic Unit: Molecular Physiology and Biophysics; Biology; Neurosurgery; Otolaryngology
Record Identifier: 9984007198602771

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