CHARACTERIZATION OF TYPE-III INTERMEDIATE FILAMENT REGULATORY PROTEINTARGET EPITOPES - S-100 (BETA AND OR ALPHA) BINDS THE N-TERMINAL HEADDOMAIN - ANNEXIN II2-P11(2) BINDS THE ROD DOMAINS/

We have investigated the interaction of S-100 proteins (beta and/or al pha) and annexin II2-p11(2) with glial fibrillary acidic protein (GFAP ) and desmin to have further information on the mechanisms whereby S-1 00 proteins and annexin II2-p11(2) affect assembly/disassembly of GFAP and desmin intermediate filaments (Ifs), Analyses were conducted on e ither native IF subunits, GFAP or desmin rod domain, or headless GFAP or desmin, Our data indicate that: (i) S-100 proteins bind to GFAP and desmin N-terminal head domain; (ii) annexin II2-p11(2) binds to GFAP rod domain; (iii) annexin II2-p11(2) does not interact with desmin nor affects desmin assembly. The present data suggest that the ability of S-100 proteins to inhibit GFAP and desmin assemblies and to promote t he disassembly of preformed GFAP and desmin Ifs depends on occupation of a site on the N-terminal head domain of these IF subunit. It is kno wn that the N-terminal head domain is critical for the progression fro m the stage of GFAP and desmin dimers/tetramers to that of large oligo mers. On the other hand, the ability of annexin II2-p11(2) to stimulat e GFAP assembly under conditions where this latter is normally hampere d (e.g., at alkaline pH values) might depend on annexin II2-p11(2)-ind uced changes in the structure of GFAP rod domain, possibly as a conseq uence of charge modifications, By contrast, the inability of annexin I I2-p11(2) to bind to desmin would depend on desmin resistance to charg e modifications.