Targeted inactivation of a developmentally regulated neural plectin isoform (plectin 1c) in mice leads to reduced motor nerve conduction velocity.
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.
Fuchs
Peter
P
Department of Biochemistry and Cell Biology, Max F Perutz Laboratories, University of Vienna, 1030 Vienna, Austria.
Zörer
Michael
M
Reipert
Siegfried
S
Rezniczek
Günther A
GA
Propst
Friedrich
F
Walko
Gernot
G
Fischer
Irmgard
I
Bauer
Jan
J
Leschnik
Michael W
MW
Lüscher
Bernhard
B
Thalhammer
Johann G
JG
Lassmann
Hans
H
Wiche
Gerhard
G
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
C495333:Plec protein, mouse; D051190:Plectin; D020033:Protein Isoforms