NZO-3 expression causes global changes to actin cytoskeleton in Madin-Darby canine kidney cells: linking a tight junction protein to Rho GTPases.
We previously demonstrated that exogenous expression of a truncated form of the tight junction protein ZO-3 affected junctional complex assembly and function. Current results indicate that this ZO-3 construct influences actin cytoskeleton dynamics more globally. We show that expression of the amino-terminal half of ZO-3 (NZO-3) in Madin-Darby canine kidney cells results in a decreased number of stress fibers and focal adhesions and causes an increased rate of cell migration in a wound healing assay. We also demonstrate that RhoA activity is reduced in NZO-3-expressing cells. We determined that ZO-3 interacts with p120 catenin and AF-6, proteins localized to the junctional complex and implicated in signaling pathways important for cytoskeleton regulation and cell motility. We also provide evidence that NZO-3 interacts directly with the C terminus of ZO-3, and we propose a model where altered interactions between ZO-3 and p120 catenin in NZO-3-expressing cells affect RhoA GTPase activity. This study reveals a potential link between ZO-3 and RhoA-related signaling events.
Wittchen
Erika S
ES
Department of Cell Biology, University of Alberta, Edmonton, Canada T6G 2H7.
Haskins
Julie
J
Stevenson
Bruce R
BR
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D004285:Dogs; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D062825:Zonula Occludens Proteins; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D000199:Actins; D002352:Carrier Proteins; D008565:Membrane Proteins; D062825:Zonula Occludens Proteins; D020741:rho GTP-Binding Proteins