Microtubule-associated protein 1B is a component of cortical Lewy bodies and binds alpha-synuclein filaments.
Lewy bodies, neuropathological hallmarks of Parkinson's disease and dementia with Lewy bodies, comprise alpha-synuclein filaments and other less defined proteins. Characterization of Lewy body proteins that interact with alpha-synuclein may provide insight into the mechanism of Lewy body formation. Double immunofluorescence labeling and confocal microscopy revealed approximately 80% of cortical Lewy bodies contained microtubule-associated protein 1B (MAP-1B) that overlapped with alpha-synuclein. Lewy bodies were isolated using an immunomagnetic technique from brain tissue of patients dying with dementia with Lewy bodies. Lewy body proteins were resolved by polyacrylamide gel electrophoresis. Immunoblotting confirmed the presence of MAP-1B and alpha-synuclein in purified Lewy bodies. Direct binding studies revealed a high affinity interaction (IC(50) approximately 20 nm) between MAP-1B and alpha-synuclein. The MAP-1B-binding sites were mapped to the last 45 amino acids of the alpha-synuclein C terminus. MAP-1B also bound in vitro assembled alpha-synuclein fibrils. Thus, MAP-1B may be involved in the pathogenesis of Lewy bodies via its interaction with monomeric and fibrillar alpha-synuclein.
Jensen
P H
PH
Department of Medical Biochemistry, University of Aarhus, DK-8000 Aarhus C, Denmark, Arpida AG, Munchenstein 4142, Switzerland. phj@biokemi.au.dk
Islam
K
K
Kenney
J
J
Nielsen
M S
MS
Power
J
J
Gai
W P
WP
D000368:Aged; D000369:Aged, 80 and over; D002458:Cell Fractionation; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D018189:Immunomagnetic Separation; D016631:Lewy Bodies / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D016253:Microscopy, Immunoelectron; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism / Q000648:ultrastructure; D051843:Synucleins; D051844:alpha-Synuclein
D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; C085284:microtubule-associated protein 1B