Versican modulates gap junction intercellular communication.
Versican is a large chondroitin sulfate proteoglycan and belongs to the family of lecticans. Versican possesses two globular domains, G1 and G3 domain, separated by a CS-attachment region. The CS-attachment region present in the middle region is divided into two spliced domains named CSalpha and beta. Alternative splicing of versican generates at least four versican isoforms named V0, V1, V2, and V3. We have successfully cloned the full-length cDNA of chick versican isoforms V1 and V2 and found that versican isoform V1 induced mesenchymal-epithelial transition in NIH3T3 cells. Mesenchymal-epithelial transition induced by V1 in NIH3T3 cells is characterized by expression of E-cadherin and occludin, two epithelial markers, and reduced expression of fibroblastic marker vimentin (Sheng et al., 2006, Mol Biol Cell. 17, 2009-2020). In the present studies, we found that versican V1 isoform not only induced cell transition, but also increased intercellular communication via gap junction channels composed of connexin proteins. Our results showed that V1 induces plasma membrane localization of connexin 43, resulting in increased cell communication. This was further confirmed by blocking assays. Gap junctions mediated the transfer of small cytoplasmic molecules and the diffusion of second messenger molecules between adjacent cells. The ability of versican in regulating gap junction implied a potential role of versican in coordinating functions.
Sheng
Wang
W
Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Dong
Haiheng
H
Lee
Daniel Y
DY
Lu
Wei-Yang
WY
Yang
Burton B
BB
D000818:Animals; D002450:Cell Communication; D002645:Chickens; D017630:Connexins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology; D017629:Gap Junctions / Q000378:metabolism*; D020868:Gene Silencing; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection; D053675:Versicans / Q000378:metabolism*
D017630:Connexins; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D053675:Versicans