Connexin45 directly binds to ZO-1 and localizes to the tight junction region in epithelial MDCK cells

FEBS Lett. 2001 Sep 7;505(1):92-6. doi: 10.1016/s0014-5793(01)02786-7.


Zonula occludens protein 1 (ZO-1) is a cytosolic tight junction protein that tethers transmembrane proteins such as occludin, claudin and junctional adhesion molecule to the actin cytoskeleton. The interaction between ZO-1 and claudin or junctional adhesion molecule occurs via the amino-terminal PSD95/Dlg/ZO-1 (PDZ) domains in ZO-1. A yeast two-hybrid screen to search for proteins that interact with the PDZ domains of ZO-1 identified connexin (Cx) 45. Cx45 interacts with the PDZ domains of ZO-1 and ZO-3, but not ZO-2, via a short C-terminal PDZ binding motif (SVWI). In transfected epithelial Madin-Darby canine kidney cells, Cx45 co-localizes with endogenous ZO-1 at or near tight junctions and co-precipitation experiments show that Cx45 and ZO-1 directly interact. Inactivating the C-terminal PDZ-binding motif in Cx45 affects its co-precipitation and co-localization with ZO-1. The growing number of connexins (i.e. Cx43 and Cx45) that can associate with ZO proteins indicate that ZO proteins may play a more general role in organizing gap junctions and/or in recruiting signaling molecules that regulate intercellular communication.

MeSH terms

  • Animals
  • Binding Sites
  • Carrier Proteins / metabolism
  • Cell Polarity
  • Cells, Cultured
  • Connexins / genetics
  • Connexins / metabolism*
  • Dogs
  • Epithelial Cells / metabolism
  • Gap Junctions / metabolism*
  • Kidney / cytology
  • Kidney / metabolism
  • Membrane Proteins / metabolism*
  • Mice
  • Mutation
  • Phosphoproteins / metabolism*
  • Protein Structure, Tertiary
  • Transfection
  • Two-Hybrid System Techniques
  • Zonula Occludens Proteins
  • Zonula Occludens-1 Protein
  • Zonula Occludens-2 Protein


  • Carrier Proteins
  • Connexins
  • Membrane Proteins
  • Phosphoproteins
  • Tjp1 protein, mouse
  • Tjp2 protein, mouse
  • Tjp3 protein, mouse
  • Zonula Occludens Proteins
  • Zonula Occludens-1 Protein
  • Zonula Occludens-2 Protein
  • connexin 45