title: Cell coupling mediated by connexin 26 selectively contributes to reduced adhesivity and increased migration.
abstract: Gap junction proteins (connexins) have crucial effects on cell motility in many systems, from migration of neural crest cells to promotion of metastatic invasiveness. Here, we show that expression of Cx26 (also known as GJB2) in HeLa cells specifically enhances cell motility in scrape wounding and sparse culture models. This effect is dependent on gap junction channels and is isotype specific [Cx26 enhances motility, whereas Cx43 (also known as GJA1) does not and Cx32 (also known as GJB1) has an intermediate effect]. The increased motility is associated with reduced cell adhesiveness, caused by loss of N-cadherin protein and RNA at the wound edge. This in turn causes a redistribution of N-cadherin-binding proteins (p120 catenin and β-catenin) to the cytosol and nucleus, respectively. The former activates Rac-1, which mediates cytoskeletal rearrangements needed for filopod extension. The latter is associated with increased expression of urokinase plasminogen activating receptor (an activator of extracellular proteases) and secretion of extracellular matrix components like collagen. Although these effects were dependent on Cx26-mediated coupling of the cells, they are not mediated by the same signal (i.e. cAMP) through which Cx26 has been shown to suppress proliferation in the same system.
authors: Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors: Srikanth R
authors: SR
authors: Polusani
authors: Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors: Edward A
authors: EA
authors: Kalmykov
authors: Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors: Anjana
authors: A
authors: Chandrasekhar
authors: Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA zucker@dyc.edu NicholsonB@uthscsa.edu.
authors: Shoshanna N
authors: SN
authors: Zucker
authors: Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA zucker@dyc.edu NicholsonB@uthscsa.edu.
authors: Bruce J
authors: 0000-0003-1649-7173
authors: BJ
authors: Nicholson
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D018920:Coculture Techniques; D000072259:Connexin 26 / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D008954:Models, Biological; D011485:Protein Binding; D014162:Transfection; D014945:Wound Healing
chemical_list: D015820:Cadherins; D000072259:Connexin 26; D000242:Cyclic AMP
keywords: Cell adhesion; Cell motility; Connexin; Gap junction