Association of ARVCF with zonula occludens (ZO)-1 and ZO-2: binding to PDZ-domain proteins and cell-cell adhesion regulate plasma membrane and nuclear localization of ARVCF

• Published in: Molecular biology of the cell 2004-12, Vol.15 (12), p.5503-5515
• Main Authors: Kausalya, P Jaya, Phua, Dominic C Y, Hunziker, Walter
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Amino Acid Sequence; Animals; Armadillo Domain Proteins; Binding Sites; Cadherins - metabolism; Cell Adhesion; Cell Adhesion Molecules - chemistry; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Line; Cell Membrane - metabolism; Cell Nucleus - metabolism; Cytoskeleton - metabolism; Dogs; Humans; Membrane Proteins - genetics; Membrane Proteins - metabolism; Molecular Sequence Data; Phosphoproteins - chemistry; Phosphoproteins - genetics; Phosphoproteins - metabolism; Protein Binding; Protein Structure, Tertiary; Protein Transport; Sequence Alignment; Zonula Occludens-1 Protein; Zonula Occludens-2 Protein
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.E04-04-0350

ARVCF, an armadillo-repeat protein of the p120(ctn) family, associates with classical cadherins and is present in adherens junctions, but its function is poorly understood. Here, we show that ARVCF interacts via a C-terminal PDZ-binding motif with zonula occludens (ZO)-1 and ZO-2. ARVCF and ZO-1 partially colocalize in the vicinity of the apical adhesion complex in polarized epithelial Madin-Darby canine kidney cells. ARVCF, ZO-1, and E-cadherin form a complex and are recruited to sites of initial cell-cell contact in sparse cell cultures. E-cadherin binding and plasma membrane localization of ARVCF require the PDZ-binding motif. Disruption of cell-cell adhesion releases ARVCF from the plasma membrane and an increased fraction of the protein localizes to the nucleus. Nuclear localization of ARVCF also requires the PDZ-binding motif and can be mediated by the PDZ domains of ZO-2. Thus, the interaction of ARVCF with distinct PDZ-domain proteins determines its subcellular localization. Interactions with ZO-1 and ZO-2, in particular, may mediate recruitment of ARVCF to the plasma membrane and the nucleus, respectively, possibly in response to cell-cell adhesion cues.