The role of nectins in different types of cell–cell adhesion

Abstract

SummaryMammalian tissues and organs are composed of different types of cells that adhere to each other homotypically (i.e. interactions between cells of the same cell type) or heterotypically (i.e. interactions between different cell types), forming a variety of cellular patterns, including mosaic patterns. At least three types of cell-cell adhesion have been observed: symmetric homotypic, asymmetric homotypic and heterotypic cell adhesions. Cadherins and nectins, which are known cell-cell adhesion molecules, mediate these cell adhesions. Cadherins comprise a family of more than 100 members, but they are primarily involved in homophilic trans-interactions (i.e. interactions between the same cadherin members) between opposing cells. By contrast, the nectin family comprises only four members, and these proteins form both homophilic and heterophilic trans-interactions (i.e. interactions between the same and different nectin members on opposing cells). In addition, heterophilic trans-interactions between nectins are much stronger than homophilic trans-interactions. Because of these unique properties, nectins have crucial roles in asymmetric homotypic cell-cell adhesion at neuronal synapses and in various types of heterotypic cell-cell adhesions. We summarize recent progress in our understanding of the biology of nectins and discuss their roles in heterotypic cell-cell adhesions, whose formation cannot be solely explained by the action of cadherins.

Enfortumab Vedotin Antibody–Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models

“…The functional significance of this observation is presently unknown, as the role of nectin-4 in normal epithelial tissue structure and morphogenesis is poorly understood. We and others hypothesize that nectin-4 plays a role in the establishment and maintenance of adherens junctions, which in normal epithelium define cell polarity, a characteristic often lost during cancer progression (12). We have attempted, but not yet succeeded, in identifying an anti-nectin-4 antibody that intrinsically modulates tumor growth.…”

“…Nectin-4 is a member of the nectin family of immunoglobulin-like adhesion molecules (10)(11)(12) that are proposed to mediate Ca 2þ -independent cell-cell adhesion via both homophilic and heterophilic trans-interactions at adherens junctions, where they recruit cadherins and modulate cytoskeleton rearrangements (12). On the basis of the differential expression of nectin-4 in bladder cancers, we developed a novel ADC, enfortumab vedotin, comprising fusion between a fully human antibody targeting nectin-4 and the potent microtubule-disrupting agent monomethyl auristatin E (MMAE).…”

De novo lumen formation and elongation in the developing nephron: a central role for afadin in apical polarity

“…Nectin/afadin complexes are also required for tight junction formation, which occurs subsequent to adherens junction formation (Fukuhara et al, 2002a;Fukuhara et al, 2002b;Ooshio et al, 2010). The nectin family consists of nectins 1 to 4, which interact on the surface of the same cell to form cis-dimers, and then interact with nectin dimers in trans on the apposing cell to form cell-cell adhesions (Harrison et al, 2012;Narita et al, 2011;Rikitake et al, 2012;SatohHorikawa et al, 2000). Afadin, initially identified as an F-actin binding protein, is the main intracellular regulator of nectins 1 to 3 (Mandai et al, 1997;Takahashi et al, 1999), and an effector of the small GTPase Rap1 (Boettner and Van Aelst, 2009).…”

Les récepteurs de nectines/nectines-likeDNAM-1 et CRTAM

“…Dans le cas des nectines, l'interaction avec l'actine se fait par l'intermédiaire de la protéine afadine (filamentous [f]-actin-binding protein). Certaines nectines sont également capables de s'associer avec d'autres molécules cytoplasmiques, telles que PAR3 (partioning defective 3 homologue) ou PICK1 (protein interacting with PRKCA1) (pour revue voir [4]). À la différence des nectines, les nectines-like ne lient pas l'afadine : elles interagissent avec l'actine via des protéines d'échafaudage de la famille des MAGuK (membrane-associated guanylate kinase) ou des protéines de la famille de la bande 4.1 1 .…”