Targeted inactivation of a developmentally regulated neural plectin isoform (plectin 1c) in mice leads to reduced motor nerve conduction velocity

Peter Fuchs, Michael Zörer, Siegfried Reipert, Günther A Rezniczek, Friedrich Propst, Gernot Walko, Irmgard Fischer, Jan Bauer, Michael W Leschnik, Bernhard Lüscher, Johann G Thalhammer, Hans Lassmann, Gerhard Wiche

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Cytolinker proteins stabilize cells mechanically, regulate cytoskeleton dynamics, and provide scaffolds for signaling molecules. For plectin, the prototype of these proteins, an unusual diversity of isoforms has been reported, which show distinct expression patterns, subcellular localizations, and functions. Plectin has been shown to have important functions in skin and muscle, but little is known about its role in neural cells. To address this issue, we generated two knock-out mouse lines, one which was selectively lacking plectin 1c (P1c), the major isoform expressed in neural cells, and another in which plectin was conditionally deleted in neuronal precursor cells. Using isoform-specific antibodies, we found P1c to be expressed late in development and to associate with postsynaptic dendrites of central nervous system neurons, motorneurons of spinal cord, sciatic nerve axons, and Schwann cells. Motor nerve conduction velocity was found significantly reduced in sciatic nerve from P1c-deficient as well as from conditional knock-out mice. This defect was traceable to an increased number of motor nerve fibers with small cross-sectional areas; the thicknesses of axons and of myelin sheaths were unaffected. This is the first report demonstrating an important role of plectin in a major nerve function.

Original languageEnglish
Pages (from-to)26502-26509
Number of pages8
JournalThe Journal of biological chemistry
Volume284
Issue number39
DOIs
Publication statusPublished - 25 Sep 2009

Keywords

  • Animals
  • Central Nervous System/metabolism
  • Female
  • Gene Targeting/methods
  • Genotype
  • Immunoblotting
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Electron
  • Microscopy, Fluorescence
  • Motor Neurons/physiology
  • Neural Conduction/physiology
  • Plectin/genetics
  • Protein Isoforms/genetics
  • Ranvier's Nodes/ultrastructure
  • Sciatic Nerve/metabolism
  • Spinal Cord/metabolism
  • Spinal Nerve Roots/ultrastructure

Cite this

Fuchs, P., Zörer, M., Reipert, S., Rezniczek, G. A., Propst, F., Walko, G., Fischer, I., Bauer, J., Leschnik, M. W., Lüscher, B., Thalhammer, J. G., Lassmann, H., & Wiche, G. (2009). Targeted inactivation of a developmentally regulated neural plectin isoform (plectin 1c) in mice leads to reduced motor nerve conduction velocity. The Journal of biological chemistry, 284(39), 26502-26509. https://doi.org/10.1074/jbc.M109.018150