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
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.