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 cytokeratin proteins. Desmin microprecipitates without vimentin or vimentin microprecipitates without desmin are not observed. The microprecipitates involving cytokeratin invariably are also positive for desmin and vimentin. Over time, the precipitates enlarge into 1- to 2-microns spheroids and then fuse into amorphous chimeric juxtanuclear masses that can occupy > 30% of the cell volume. Concurrently, first the vimentin and then the cytokeratin networks are resorbed. The chimeric precipitates are not recognized or marked for degradation by the lysosomal system. Ultimately the cell nucleus fragments and the cell dies. Similar protein complexes 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 work.
Yu
K R
KR
Department of Cell Biology, University of Pennsylvania School of Medicine, Philadelphia 19104-6059.
Hijikata
T
T
Lin
Z X
ZX
Sweeney
H L
HL
Englander
S W
SW
Holtzer
H
H
D000544:Alzheimer Disease / Q000473:pathology; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology; D000818:Animals; D002467:Cell Nucleus / Q000473:pathology*; D002478:Cells, Cultured; D011232:Chemical Precipitation; D003893:Desmin / Q000235:genetics / Q000378:metabolism*; D007382:Intermediate Filaments / Q000378:metabolism*; D007633:Keratins / Q000378:metabolism*; D007614:Macropodidae; D014746:Vimentin / Q000378:metabolism*
D003893:Desmin; D014746:Vimentin; D007633:Keratins