Regulation of the intermediate filament protein nestin at rodent neuromuscular junctions by innervation and activity

Kang, H., Tian, L., Son, Y. J., Zuo, Y., Procaccino, D., Love, F., Hayworth, C., Trachtenberg, J., Mikesh, M., Sutton, L., Ponomareva, O., Mignone, J., Enikolopov, G., Rimer, M., Thompson, W. (May 2007) Regulation of the intermediate filament protein nestin at rodent neuromuscular junctions by innervation and activity. Journal of Neuroscience, 27 (22). pp. 5948-5957. ISSN 0270-6474

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URL: https://www.ncbi.nlm.nih.gov/pubmed/17537965
DOI: 10.1523/JNEUROSCI.0621-07.2007

Abstract

The intermediate filament nestin is localized postsynaptically at rodent neuromuscular junctions. The protein forms a filamentous network beneath and between the synaptic gutters, surrounds myofiber nuclei, and is associated with Z-discs adjacent to the junction. In situ hybridization shows that nestin mRNA is synthesized selectively by synaptic myonuclei. Although weak immunoreactivity is present in myelinating Schwann cells that wrap the preterminal axon, nestin is not detected in the terminal Schwann cells (tSCs) that cover the nerve terminal branches. However, after denervation of muscle, nestin is upregulated in tSCs and in SCs within the nerve distal to the lesion site. In contrast, immunoreactivity is strongly downregulated in the muscle fiber. Transgenic mice in which the nestin neural enhancer drives expression of a green fluorescent protein (GFP) reporter show that the regulation in SCs is transcriptional. However, the postsynaptic expression occurs through enhancer elements distinct from those responsible for regulation in SCs. Application of botulinum toxin shows that the upregulation in tSCs and the loss of immunoreactivity in muscle fibers occurs with blockade of transmitter release. Extrinsic stimulation of denervated muscle maintains the postsynaptic expression of nestin but does not affect the upregulation in SCs. Thus, a nestin-containing cytoskeleton is promoted in the postsynaptic muscle fiber by nerve-evoked muscle activity but suppressed in tSCs by transmitter release. Nestin antibodies and GFP driven by nestin promoter elements serve as excellent markers for the reactive state of SCs. Vital imaging of GFP shows that SCs grow a dynamic set of processes after denervation.

Item Type: Paper
Uncontrolled Keywords: transgenic synaptic gene expression terminal Schwann cell denervation paralysis muscle stimulation SCHWANN-CELLS SKELETAL-MUSCLE IN-VIVO POSTSYNAPTIC MEMBRANE ELECTRON-MICROSCOPY NEURAL REGULATION NERVOUS-SYSTEM GROWTH-FACTOR STEM-CELLS EXPRESSION
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > nestin
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > schwann cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > schwann cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > schwann cells

organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse
CSHL Authors:
Communities: CSHL labs > Enikopolov lab
Depositing User: CSHL Librarian
Date: May 2007
Date Deposited: 11 Nov 2011 16:24
Last Modified: 01 Mar 2017 15:34
Related URLs:
URI: http://repository.cshl.edu/id/eprint/23056

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