Axonal transport of synucleins is mediated by all rate components.
Synucleins are abundant nerve terminal proteins of hitherto unknown function. In diseases with Lewy bodies, human alpha-synuclein concentrates in these lesions in the cell body and mutations in alpha-synuclein lead to heritable Parkinson's disease with Lewy bodies. This indicates that changes in the normal metabolism and axonal transport of alpha-synuclein is perturbed in these diseases. To investigate the normal axonal transport of synucleins we studied the rat visual system by nerve crush operations and metabolic labelling of the retinal ganglion cells followed by immunoprecipitation of nerve segments. We found by immunofluorescence microscopy of the crush-operated nerves that synucleins are transported by fast antero- and retrograde transport and colocalize with synaptophysin and SNAP-25 around the lesion. The metabolic labelling studies demonstrated that synucleins were moved through the nerve with all the rate components, the fast component and the slow components a and b, with component b predominating. Two-dimensional gel electrophoresis revealed that both alpha- and beta-synuclein migrate through the nerve by slow component b in a ratio of 2:1.
Jensen
P H
PH
Department of Medical Biochemistry, University of Aarhus, Denmark. phj@biokemi.au.dk
Li
J Y
JY
Dahlström
A
A
Dotti
C G
CG
D000818:Animals; D000911:Antibodies, Monoclonal; D001370:Axonal Transport / Q000502:physiology*; D015180:Electrophoresis, Gel, Two-Dimensional; D005455:Fluorescent Antibody Technique; D008297:Male; D008565:Membrane Proteins; D009409:Nerve Crush; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D009900:Optic Nerve / Q000502:physiology*; D017729:Presynaptic Terminals / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016708:Synaptophysin / Q000032:analysis / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25; D051843:Synucleins; D051844:alpha-Synuclein; D051846:beta-Synuclein
D000911:Antibodies, Monoclonal; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C494210:Snap25 protein, rat; C497606:Snca protein, rat; C497609:Sncb protein, rat; D016708:Synaptophysin; D050825:Synaptosomal-Associated Protein 25; D051843:Synucleins; D051844:alpha-Synuclein; D051846:beta-Synuclein