A novel splice variant of occludin deleted in exon 9 and its role in cell apoptosis and invasion.
The tight junction protein occludin participates in cell adhesion and migration and has been shown to possess antitumorigenic properties; however, the exact mechanism underlying these effects is poorly understood. In liver cell lines, we identified an occludin splice variant deleted in exon 9 (Occ(DeltaE9)). Furthermore, comparison analysis of wild-type occludin (Occ(WT)) and Occ(DeltaE9) revealed that exon 9 played important roles in the induction of mitochondria-mediated apoptosis and the inhibition of invasion, along with the downregulation of matrix metalloproteinase expression. In addition, by using the calcium indicator X-rhod-1, and the inositol trisphosphate receptor inhibitor 2-aminoethoxydiphenyl borate, we found that Occ(WT) but not Occ(DeltaE9) increased calcium release from the endoplasmic reticulum. In conclusion, our results showed that occludin mediates apoptosis and invasion by elevating the cytoplasmic calcium concentration and that exon 9 of occludin is an important region that mediates these effects.
Gu
Jin-Mo
JM
Department of Biological Sciences and Seoul National University, 56-1 Shillim-dong, Kwanak-gu, Seoul, Korea.
Lim
Seung Oe
SO
Park
Young Min
YM
Jung
Guhung
G
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D019175:DNA Methylation; D005091:Exons; D020868:Gene Silencing; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D062793:Occludin; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion
D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D002118:Calcium