The 14-3-3 protein epsilon isoform expressed in reactive astrocytes in demyelinating lesions of multiple sclerosis binds to vimentin and glial fibrillary acidic protein in cultured human astrocytes.
The 14-3-3 protein family consists of acidic 30-kd proteins expressed at high levels in neurons of the central nervous system. Seven isoforms form a dimeric complex that acts as a molecular chaperone that interacts with key signaling components. Recent studies indicated that the 14-3-3 protein identified in the cerebrospinal fluid of various neurological diseases including multiple sclerosis (MS) is a marker for extensive brain destruction. However, it remains unknown whether the 14-3-3 protein plays an active role in the pathological process of MS. To investigate the differential expression of seven 14-3-3 isoforms in MS lesions, brain tissues of four progressive cases were immunolabeled with a panel of isoform-specific antibodies. Reactive astrocytes in chronic demyelinating lesions intensely expressed beta, epsilon, zeta, eta, and sigma isoforms, among which the epsilon isoform is a highly specific marker for reactive astrocytes. Furthermore, protein overlay, mass spectrometry, immunoprecipitation, and double-immunolabeling analysis showed that the 14-3-3 protein interacts with both vimentin and glial fibrillary acidic protein in cultured human astrocytes. These results suggest that the 14-3-3 protein plays an organizing role in the intermediate filament network in reactive astrocytes at the site of demyelinating lesions in MS.
Satoh
Jun-Ichi
J
Department of Immunology, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan. satoj@ncnp.go.jp.
Yamamura
Takashi
T
Arima
Kunimasa
K
D048948:14-3-3 Proteins; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001344:Autopsy; D002478:Cells, Cultured; D003711:Demyelinating Diseases / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005333:Fetus / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D011233:Precipitin Tests; D020033:Protein Isoforms / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism*
D048948:14-3-3 Proteins; D005904:Glial Fibrillary Acidic Protein; D020033:Protein Isoforms; D014746:Vimentin; D014446:Tyrosine 3-Monooxygenase