IN-VITRO POLYMERIZATION OF EMBRYONIC MAP-2C AND FRAGMENTS OF THE MAP-2 MICROTUBULE-BINDING REGION INTO STRUCTURES RESEMBLING PAIRED HELICALFILAMENTS

Citation
Ma. Deture et al., IN-VITRO POLYMERIZATION OF EMBRYONIC MAP-2C AND FRAGMENTS OF THE MAP-2 MICROTUBULE-BINDING REGION INTO STRUCTURES RESEMBLING PAIRED HELICALFILAMENTS, The Journal of biological chemistry, 271(51), 1996, pp. 32702-32706
Citations number
28
Categorie Soggetti
Biology
ISSN journal
00219258
Volume
271
Issue
51
Year of publication
1996
Pages
32702 - 32706
Database
ISI
SICI code
0021-9258(1996)271:51<32702:IPOEMA>2.0.ZU;2-N
Abstract
The microtubule-associated protein Tau is widely regarded as the princ ipal component of paired helical filaments comprising Alzheimer neurof ibrillary tangles. Tau fragments containing the non identical repeat r egion formed structures resembling paired helical filaments (Schweers, O., Mandelkow, M., Biernat, J., and Mandelkom, E. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 8463-8467). MAP-5, the other structurally rela ted neuronal microtubule-associated protein, has not been implicated i n paired helical filament formation. We now describe the assembly of p aired helical filament-like structures from MAP-S polypeptides contain ing only 100 residues. A dimeric species, stabilized by an interchain disulfide, appears to be involved in the assembly reaction. We also in vestigated the polymerization of embryonic MAP-2c, which, except for i ts microtubule binding region, is structurally distinct from Tau. Full -length MAP-2c formed paired helical filament-like polymers. Polymeriz ed MAP-2c and the microtubule binding region fragment readily bound th ioflavin-S, a dye that stains paired helical filaments in the histoche mical diagnosis of Alzheimer's disease. Our unprecedented finding that a small MAP-2 microtubule binding region fragment and MAP-2c can form structures resembling straight filaments or Pronase-treated paired he lical filaments raises fundamental questions concerning the role of MA P-2 in the pathobiology of Alzheimer disease.