title: The specific fates of tight junction proteins in apoptotic epithelial cells.
abstract: The polarized morphology of epithelial cells depends on the establishment and maintenance of characteristic intercellular junctions. The dramatic morphological changes observed in apoptotic epithelial cells were ascribed at least in part to the specific fragmentation of components of adherens junctions and desmosomes. Little, however, is known about tight junctions during apoptosis. We have found that after induction of apoptosis in epithelial cells, tight junction proteins undergo proteolytic cleavage in a distinctive manner correlated with a disruption of tight junctions. The transmembrane protein occludin and, likewise, the cytoplasmic adaptor proteins ZO-1 and ZO-2 are fragmented by caspase cleavage. In addition, occludin is cleaved at an extracellular site by a metalloproteinase. The caspase cleavage site in occludin was mapped C-terminally to Asp(320) within the C-terminal cytoplasmic domain. Mutagenesis of this site efficiently blocked fragmentation. In the presence of caspase and/or metalloproteinase inhibitors, fragmentation of occludin, ZO-1 and ZO-2 was blocked and cellular morphology was almost fully preserved. Interestingly, two members of the claudin family of transmembrane tight junction proteins exhibited a different behavior. While the amount of claudin-2 protein was reduced similarly to occludin, ZO-1 and ZO-2, claudin-1 was either fully preserved or was even increased in apoptotic cells.
authors.affiliation: Institute of Clinical Chemistry and Pathobiochemistry, Charité - Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bojarski
authors.forename: Jörg
authors.initials: J
authors.lastname: Weiske
authors.forename: Torsten
authors.initials: T
authors.lastname: Schöneberg
authors.forename: Werner
authors.initials: W
authors.lastname: Schröder
authors.forename: Joachim
authors.initials: J
authors.lastname: Mankertz
authors.forename: Jörg-Dieter
authors.initials: JD
authors.lastname: Schulzke
authors.forename: Peter
authors.initials: P
authors.lastname: Florian
authors.forename: Michael
authors.initials: M
authors.lastname: Fromm
authors.forename: Rudolf
authors.initials: R
authors.lastname: Tauber
authors.forename: Otmar
authors.initials: O
authors.lastname: Huber
mesh_terms: D000818:Animals; D017209:Apoptosis; D001224:Aspartic Acid / Q000737:chemistry; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D053938:DNA Fragmentation; D018076:DNA, Complementary / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008856:Microscopy, Fluorescence; D016296:Mutagenesis; D016297:Mutagenesis, Site-Directed; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D019108:Tight Junctions / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein
chemical_list: D018076:DNA, Complementary; D008565:Membrane Proteins; D062793:Occludin; D010750:Phosphoproteins; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein; D001224:Aspartic Acid; D020169:Caspases