title: The proteins synaptotagmin and syntaxin are not general targets of Lambert-Eaton myasthenic syndrome autoantibody.
abstract: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune neuromuscular disease in which impairment of Ca2+ entry into the nerve ending and consequent impaired release of acetylcholine (ACh) results in muscle weakness. The identity of the primary antigenic target molecule(s) of the autoantibodies is uncertain. Electrophysiological studies and 45Ca2+ uptake studies implicate a direct effect on the Ca2+ channel complex at the motor nerve terminal. Some recent studies, however, suggest a more indirect interference caused by binding of autoantibodies to synaptotagmin or syntaxin, molecules presumed to be involved in docking and/or coupling the synaptic vesicles to the Ca2+ channels in the active zone for vesicle exocytosis and transmitter release. Western blot analyses of rat and human brain membrane proteins and pure recombinant synaptotagmin and syntaxin were used to examine directly the targets of LEMS autoantibodies and determine specifically whether or not synaptotagmin and/or syntaxin were general targets in LEMS. IgG from 14 patients with LEMS was used to probe western blots of gels containing synaptotagmin, syntaxin, rat synaptosomal proteins, and human brain membrane proteins. Several similar immunoreactive bands were observed using both rat and human brain membranes. These include high-molecular-weight protein bands whose size would be consistent with being components of Ca2+ channels. No reactive component was observed against either syntaxin or synaptotagmin in IgG of the 14 LEMS patients. However, both human and rat brain membranes contain proteins recognized by antibodies directed against synaptotagmin or syntaxin, indicating their immunologic relatedness and evolutionary conservation. These results suggest that large-molecular-weight proteins consistent with being Ca2+ channel subunits rather than syntaxin and synaptotagmin are general targets of LEMS autoantibodies.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824-1317.
authors.forename: R K
authors.initials: RK
authors.lastname: Hajela
authors.forename: W D
authors.initials: WD
authors.lastname: Atchison
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001344:Autopsy; D015153:Blotting, Western; D002135:Calcium-Binding Proteins; D006801:Humans; D015624:Lambert-Eaton Myasthenic Syndrome / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000276:immunology*; D050765:Qa-SNARE Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000276:immunology; D050857:Synaptotagmins
chemical_list: D001324:Autoantigens; D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D050857:Synaptotagmins