title: Targeted inactivation of a developmentally regulated neural plectin isoform (plectin 1c) in mice leads to reduced motor nerve conduction velocity.
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.
authors.affiliation: Department of Biochemistry and Cell Biology, Max F Perutz Laboratories, University of Vienna, 1030 Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Fuchs
authors.forename: Michael
authors.initials: M
authors.lastname: Zörer
authors.forename: Siegfried
authors.initials: S
authors.lastname: Reipert
authors.forename: Günther A
authors.initials: GA
authors.lastname: Rezniczek
authors.forename: Friedrich
authors.initials: F
authors.lastname: Propst
authors.forename: Gernot
authors.initials: G
authors.lastname: Walko
authors.forename: Irmgard
authors.initials: I
authors.lastname: Fischer
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.forename: Michael W
authors.initials: MW
authors.lastname: Leschnik
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lüscher
authors.forename: Johann G
authors.initials: JG
authors.lastname: Thalhammer
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wiche
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D005260:Female; D018390:Gene Targeting / Q000379:methods*; D005838:Genotype; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009046:Motor Neurons / Q000502:physiology*; D009431:Neural Conduction / Q000502:physiology*; D051190:Plectin / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011901:Ranvier's Nodes / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000378:metabolism / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism; D013126:Spinal Nerve Roots / Q000648:ultrastructure
chemical_list: C495333:Plec protein, mouse; D051190:Plectin; D020033:Protein Isoforms