Similar and differential behaviour between the nectin‐afadin‐ponsin and cadherin‐catenin systems during the formation and disruption of the polarized junctional alignment in epithelial cells

Abstract

Background: We have recently identi®ed a novel cellcell adhesion system, named NAP system, which is localized at cadherin-based cell-cell adherens junctions (AJs). The NAP system is composed of at least nectin, afadin and ponsin. Nectin is an immunoglobulin-like cell adhesion molecule. Afadin is an actin ®lament-binding protein which associates nectin with the actin cytoskeleton. Ponsin is an afadin-binding protein which furthermore binds to vinculin and provides a possible linkage of nectin-afadin to cadherin-catenin through vinculin. We compared here the behaviour of the NAP and cadherin-catenin systems during the formation and disruption of the polarized junctional alignment in epithelial cells.

Localization of mLin-7 at nectin-based cell–cell junctions

“…At the next stage, small cell ± cell junctions are formed at the tips of these cellular protrusions, which are regarded as spot-like primordial junctions as previously reported (Yonemura et al, 1995). Nectin-2 is concentrated at these small contact sites (Asakura et al, 1999). We con®rmed here these earlier observations.…”

“…Wound healing assay of MTD-1A cells was performed as described (Ando-Akatsuka et al, 1999;Asakura et al, 1999). Brie¯y, MTD-1A cells (5.0610 5 cells) were seeded on a 18-mm glass coverslip (Matsunami, Osaka, Japan) and cultured for about 48 h to be con¯uent.…”

“…The cadherin ± catenin and nectin ± afadin systems colocalize at the primordial junctions (Asakura et al, 1999). The nectin ± afadin system has a potency to recruit the E-cadherin ± bcatenin complex .…”

CLMP, a Novel Member of the CTX Family and a New Component of Epithelial Tight Junctions

“…An interesting finding was that CLMP was recruited to plasma membrane protrusions and early cellular contacts between subconfluent cells. Earlier studies have shown that ZO-1 co-localizes together with cadherin, nectin and AF-6 in such primordial junctions (36,37). As polarization proceeds, claudin and occludin gradually accumulate at the ZO-1 positive, spot-like junctions, to form belt-like TJs.…”

Restoration of E-cadherin-based cell–cell adhesion by overexpression of nectin in HSC-39 cells, a human signet ring cell gastric cancer cell line

“…We have obtained several lines of evidence that the nectin-afadin system plays an important role in the formation of AJs in cooperation with the E-cadherincatenin system: (1) the nectin-afadin system is strictly con®ned to AJs, which are undercoated with F-actin bundles in polarized epithelial cells, whereas the Ecadherin-catenin system is more widely distributed from AJs to the basal area along the lateral membrane (Mandai et al, 1997;Takahashi et al, 1999); (2) studies using afadin (7/7) mice and (7/7) embryoid bodies indicate that the proper organization of AJs and TJs are markedly impaired in epithelial cells (Ikeda et al, 1999); (3) cadherin-de®cient L ®broblasts stably expressing nectin-1 (nectin-1-L cells) form cell ± cell adhesion in an E-cadherin-independent manner, and the nectin-1-afadin system recruits the E-cadherincatenin system without the formation of the transdimmer of E-cadherin to the nectin-1-based cell ± cell adhesion formed between nectin-1-L cells and L cells stably expressing both E-cadherin and nectin-1 (nectin-1-EL cells) ; and (4) at the initial stage during the formation of AJs and TJs, primordial spot-like cell ± cell junctions are ®rst formed at the tips of the cellular protrusions radiating from adjacent cells (Yonemura et al, 1995;Ando-Akatsuka et al, 1999;Adams et al, 1998;Vasioukhin et al, 2000), and the E-cadherin-catenin and nectin-afadin systems colocalize to the primordial junctions where claudin is not concentrated (Ando-Akatsuka et al, 1999;Asakura et al, 1999;. Consistent with our results, nectin-1 has recently been determined by positional cloning to be responsible for cleft lip/palate-ectodermal dysplasia, which is characterized by cleft lip/palate, syndactyly, mental retardation, and ectodermal dysplasia (Suzuki et al, 2000).…”