Syncoilin modulates peripherin filament networks and is necessary for large-calibre motor neurons.
Syncoilin is an atypical type III intermediate filament (IF) protein, which is expressed in muscle and is associated with the dystrophin-associated protein complex. Here, we show that syncoilin is expressed in both the central and peripheral nervous systems. Isoform Sync1 is dominant in the brain, but isoform Sync2 is dominant in the spinal cord and sciatic nerve. Peripherin is a type III IF protein that has been shown to colocalise and interact with syncoilin. Our analyses suggest that syncoilin might function to modulate formation of peripherin filament networks through binding to peripherin isoforms. Peripherin is associated with the disease amyotrophic lateral sclerosis (ALS), thus establishing a link between syncoilin and ALS. A neuronal analysis of the syncoilin-null mouse (Sync(-/-)) revealed a reduced ability in accelerating treadmill and rotarod tests. This phenotype might be attributable to the impaired function of extensor digitorum longus muscle and type IIb fibres caused by a shift from large- to small-calibre motor axons in the ventral root.
Clarke
W Thomas
WT
MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3PT, UK.
Edwards
Ben
B
McCullagh
Karl J A
KJ
Kemp
Matthew W
MW
Moorwood
Catherine
C
Sherman
Diane L
DL
Burgess
Matthew
M
Davies
Kay E
KE
D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D064531:Peripherins; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D012584:Sciatic Nerve / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism
D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; D064531:Peripherins; D020033:Protein Isoforms; C503784:SYNC protein, human; C503782:Sync protein, mouse