TRUNCATED DESMIN IN PTK2 CELLS INDUCES DESMIN VIMENTIN CYTOKERATIN COPRECIPITATION, INVOLUTION OF INTERMEDIATE FILAMENT NETWORKS, AND NUCLEAR FRAGMENTATION - A MODEL FOR MANY DEGENERATIVE DISEASES

The earliest expression of truncated desmin in transfected PtK2 cells results in the formation of dispersed microprecipitates containing not only the truncated desmin, but also endogenous vimentin and cytokerat in proteins. Desmin microprecipitates without vimentin or vimentin mic roprecipitates without desmin are not observed. The microprecipitates involving cytokeratin invariably are also positive for desmin and vime ntin. Over time, the precipitates enlarge into 1- to 2-mum spheroids a nd then fuse into amorphous chimeric juxtanuclear masses that can occu py >30% of the cell volume. Concurrently, first the vimentin and then the cytokeratin networks are resorbed. The chimeric precipitates are n ot recognized or marked for degradation by the lysosomal system. Ultim ately the cell nucleus fragments and the cell dies. Similar protein co mplexes appear in many human and animal pathologies, suggesting that a similar protein-precipitation sequence initiated by the introduction of a mutationally or environmentally altered protein molecule is at wo rk.