TRUNCATED DESMIN IN PTK2 CELLS INDUCES DESMIN VIMENTIN CYTOKERATIN COPRECIPITATION, INVOLUTION OF INTERMEDIATE FILAMENT NETWORKS, AND NUCLEAR FRAGMENTATION - A MODEL FOR MANY DEGENERATIVE DISEASES
Kr. Yu et al., TRUNCATED DESMIN IN PTK2 CELLS INDUCES DESMIN VIMENTIN CYTOKERATIN COPRECIPITATION, INVOLUTION OF INTERMEDIATE FILAMENT NETWORKS, AND NUCLEAR FRAGMENTATION - A MODEL FOR MANY DEGENERATIVE DISEASES, Proceedings of the National Academy of Sciences of the United Statesof America, 91(7), 1994, pp. 2497-2501
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.