Inhibition of cell movement and proliferation by cell–cell contact-induced interaction of Necl-5 with nectin-3

Fujito, Tsutomu; Ikeda, Wataru; Kakunaga, Shigeki; Minami, Yasunori; Kajita, Mihoko; Sakamoto, Yasuhisa; Monden, Morito; Takai, Yoshimi

doi:10.1083/jcb.200501090

Cited by 97 publications

(126 citation statements)

References 35 publications

(70 reference statements)

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“…Upon cell collision, Necl-5 at the leading edge of one cell first trans-interacts with nectin-3, which is localized diffusely on the plasma membrane of another moving cell (13). This trans-interaction of nectin-3 with Necl-5 then induces the interaction of nectin-3 with afadin.…”

Section: Discussionmentioning

confidence: 99%

“…Afadin is less likely to interact with nectins at the leading edge but is critical for the determination of directionality of cell movement (4 In addition, Necl-5 is necessary for the PDGF-induced proliferation of NIH3T3 cells in cooperation with the PDGF receptor and integrin ␣ v ␤ 3 (8,12). Upon contact of moving and proliferating NIH3T3 cells, Necl-5, which is in the complex with the PDGF receptor and integrin ␣ v ␤ 3 at the leading edge, first interacts in trans with nectin-3 (13). This interaction then causes the down-regulation of Necl-5 by its endocytosis and eventually stops proliferation and movement.…”

mentioning

confidence: 99%

“…This is one of the mechanisms of so-called contact inhibition of cell movement and proliferation (14,15). The PDGF receptor and integrin ␣ v ␤ 3 remain on the plasma membrane and then may form a complex with nectin-1 and/or nectin-3, finally recruiting N-cadherin to form AJs (13).…”

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confidence: 99%

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Cooperative Role of Nectin-Nectin and Nectin-Afadin Interactions in Formation of Nectin-based Cell-Cell Adhesion

Kurita

Ogita²,

Takai

2011

Journal of Biological Chemistry

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The nectin cell adhesion molecules interact in trans with each other through their extracellular regions and with afadin through their cytoplasmic tails, forming adherens junctions in cooperation with cadherins. In a single cell, Necl-5 (nectin-like molecule-5) localizes at the leading edge and regulates directional cell movement in response to a chemoattractant. In such a single cell, afadin also localizes at the leading edge without interacting with nectins or Necl-5. It remains unknown how the nectin-nectin and nectin-afadin interactions are initiated when moving cells contact each other to initiate the formation of adherens junctions. We show here that the Necl-5-nectin interaction induced by cell-cell contact enhances the nectin-afadin interaction. This interaction then enhances the nectin-nectin interaction, which further enhances the nectin-afadin interaction in a positive feedback manner. Thus, the Necl-5-nectin, nectin-nectin, and nectin-afadin interactions cooperatively increase the clustering of the nectin-afadin complex at the cellcell contact sites, promoting the formation of the nectin-based cell-cell adhesion.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Cooperative Role of Nectin-Nectin and Nectin-Afadin Interactions in Formation of Nectin-based Cell-Cell Adhesion

Kurita

Ogita²,

Takai

2011

Journal of Biological Chemistry

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“…PVR, a prototypical Nectin/Necl family member, is notable among the nectin/Necl family as it not only provides heterophilic interactions with other nectin family members, such as nectin-3 (17,18), but also it interacts with IgSF molecules on immune lymphocytes such as TIGIT, CD226 (also known as DNAM-1) (19), and CD96 (20) to regulate immune responses (21). Ligation of PVR induces tyrosine phosphorylation of the PVR immunoreceptor tyrosine-based inhibitory motif (ITIM) domain and recruitment of Src kinases and SHP-2 (SH2-domain-containing tyrosine phosphatase-2) (2,4,(22)(23)(24).…”

mentioning

confidence: 99%

Structure of TIGIT immunoreceptor bound to poliovirus receptor reveals a cell–cell adhesion and signaling mechanism that requires cis-trans receptor clustering

Stengel¹,

Harden-Bowles²,

Yu³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

157

159

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Nectins (nectin1-4) and Necls ] are Ig superfamily cell adhesion molecules that regulate cell differentiation and tissue morphogenesis. Adherens junction formation and subsequent cell-cell signaling is initiated by the assembly of higher-order receptor clusters of cognate molecules on juxtaposed cells. However, the structural and mechanistic details of signaling cluster formation remain unclear. Here, we report the crystal structure of poliovirus receptor (PVR)/Nectin-like-5/CD155) in complex with its cognate immunoreceptor ligand T-cell-Ig-and-ITIM-domain (TIGIT). The TIGIT/ PVR interface reveals a conserved specific "lock-and-key" interaction. Notably, two TIGIT/PVR dimers assemble into a heterotetramer with a core TIGIT/TIGIT cis-homodimer, each TIGIT molecule binding one PVR molecule. Structure-guided mutations that disrupt the TIGIT/ TIGIT interface limit both TIGIT/PVR-mediated cell adhesion and TIGIT-induced PVR phosphorylation in primary dendritic cells. Our data suggest a cis-trans receptor clustering mechanism for cell adhesion and signaling by the TIGIT/PVR complex and provide structural insights into how the PVR family of immunoregulators function.N ectins (nectin1-4) and nectin-like (Necl1-5) molecules are members of the large Ig superfamily (IgSF) of cell-surface receptors that play central roles in cell adhesion, cell movement, proliferation, and survival and contribute to the morphogenesis and differentiation of many cell and tissue types by inducing an intracellular signaling cascade (1-5). Nectins and Necls can function as both ligands and receptors and therefore are able to signal bidirectionally into juxtaposed cells (3,6). To mediate the formation of cell adherens junctions, a model suggests that the extracellular domains of these molecules form ligand-dependent homo-or heterodimers in trans (between molecules located on the same or opposite cell surfaces, respectively) and lateral homodimers in cis, creating a tight network of nectin zippers between juxtaposed cells (7,8). To date, structural and functional studies suggest a mechanism whereby the cis-homodimerization of a receptor on the same cell surface is followed by the formation of a trans-dimer between juxtaposed cells using identical protein interfaces. This assembly is noteworthy because it requires a rearrangement and breakup of the cis-homodimer followed by a transdimerization across the adherens junction. The cis-trans clustering is then initiated through another unknown protein interface, likely involving a different receptor domain.Several high-affinity homophilic trans-interactions have been described in detail for nectins/Necls and similar molecules (8-13). However, the structure and function of the presumably weaker lateral homophilic cis-dimers in cell adhesion and their role in intracellular signaling is not known. Because all structures solved to date are homodimers, it is unclear if they represent the cisor the trans-state. Thus, the question of how cis-trans heterodimerization drives cell adhesion and intracellular sign...

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“…Boyden Chamber Assay-The Boyden chamber assay was performed as described previously (27). Falcon TM cell culture inserts (8.0-m pores; BD Biosciences) were coated with 3 g/ml vitronectin at 37°C for 1 h. The inserts were then blocked with 1% BSA at 37°C for 30 min.…”

Section: Methodsmentioning

confidence: 99%

Role of Scaffold Protein Afadin Dilute Domain-interacting Protein (ADIP) in Platelet-derived Growth Factor-induced Cell Movement by Activating Rac Protein through Vav2 Protein

Fukumoto

Kurita

Takai

et al. 2011

Journal of Biological Chemistry

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Inhibition of cell movement and proliferation by cell–cell contact-induced interaction of Necl-5 with nectin-3

Cited by 97 publications

References 35 publications

Cooperative Role of Nectin-Nectin and Nectin-Afadin Interactions in Formation of Nectin-based Cell-Cell Adhesion

Cooperative Role of Nectin-Nectin and Nectin-Afadin Interactions in Formation of Nectin-based Cell-Cell Adhesion

Structure of TIGIT immunoreceptor bound to poliovirus receptor reveals a cell–cell adhesion and signaling mechanism that requires cis-trans receptor clustering

Role of Scaffold Protein Afadin Dilute Domain-interacting Protein (ADIP) in Platelet-derived Growth Factor-induced Cell Movement by Activating Rac Protein through Vav2 Protein

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