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 CSa and b. 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. J. Cell. Physiol. 211: 213–219, 2007.© 2007 Wiley-Liss, Inc.

Versican is a large aggregating chondroitin sulfate proteoglycan and belongs to the family of lectican (Aspberg et al., 1997; Yamaguchi, 2000). Versican possesses two globular domains, the N-terminal G1 domain and the C-terminal G3 domain, as well as chondroitin sulfate (CS) attachment sequence that are divided into two spliced domains named CSaandb. Alternative splicing of versican generates at least four versican isoforms: V0, V1, V2, and V3 (Ito et al., 1995; Zako et al., 1997; Lemire et al., 1999). V0 contains both CSaandb; V1 and V2 possess only CSb and a, respectively, and V3 contains neither CSa nor b. The G1 domain of versican binds hyaluronan (LeBaron et al., 1992; Matsumoto et al., 2003), while the G3 domain not only interacts with extracellular matrix (ECM) proteins (Zheng et al., 2004a, b; Wu et al., 2005b), but also interacts with sulfated glycolipid (Miura et al., 1999). Interaction of versican with ECM and cell surface proteins is believed to provide structural integrity to tissues and exert a profound effect on cell shape and behavior, including cell adhesion, spreading, migration, proliferation, and differentiation (Ingber and Folkman, 1989; Cattaruzza et al., 2004; Wu et al., 2004b, 2005a; Xiang et al., 2006; Zheng et al., 2006).