Disease relevance of Mllt4

• We studied here a role of the interaction of nectin-1alpha with afadin in entry and/or cell-cell spread of HSV-1 [1].
• Requirement of interaction of nectin-1alpha/HveC with afadin for efficient cell-cell spread of herpes simplex virus type 1 [1].
• Of the five MAbs, three (AB9, AF6 and AG6) recognized the IHNV G protein, and the other two (AB7 and BC2) recognized the 90 kDa protein [2].

High impact information on Mllt4

• Nectin is an immunoglobulin-like adhesion molecule, and afadin is an actin filament-binding protein that connects nectin to the actin cytoskeleton [3].
• The nectin-afadin system is a novel cell-cell adhesion system that organizes adherens junctions cooperatively with the cadherin-catenin system in epithelial cells [3].
• We have isolated a novel actin filament-binding protein, named afadin, localized at cadherin-based cell-cell adherens junctions (AJs) in various tissues and cell lines [4].
• PRR and afadin were colocalized at cadherin-based cell-cell AJs in various tissues and cell lines [4].
• Afadin has one PDZ domain, three proline-rich regions, and one actin filament-binding domain [4].

Biological context of Mllt4

• Afadin: A key molecule essential for structural organization of cell-cell junctions of polarized epithelia during embryogenesis [5].
• Nectins are Ca2+-independent immunoglobulin-like cell adhesion molecules connected to the actin cytoskeleton through afadin [6].
• Here, we examined the cellular localization of nectins and afadin throughout primitive streak, neural plate, and early organogenesis stages of mouse development [6].
• As cell-cell junctions are important in morphogenesis, we generated a null mutation in the murine Af6 locus to test the hypothesis that lack of AF-6 function would cause epithelial abnormalities [7].
• However, nectin-2alpha-DeltaC showed cis dimerization and trans interaction, both of which did not require the interaction of nectin-2alpha with afadin [8].

Anatomical context of Mllt4

• Nectins are associated with the actin cytoskeleton through afadin, of which the PDZ domain binds to nectins through their C-terminal four amino acids [9].
• Cell-cell AJs and tight junctions were improperly organized in the ectoderm of afadin(-/-) mice and embryoid bodies [5].
• In wild-type mice at embryonic days 6.5-8.5, afadin was highly expressed in the embryonic ectoderm and the mesoderm, but hardly detected in the extraembryonic regions such as the visceral endoderm [5].
• To explore the function of afadin in cell-cell adhesion during embryogenesis, we generated afadin(-/-) mice and embryonic stem cells [5].
• Afadin(-/-) mice showed developmental defects at stages during and after gastrulation, including disorganization of the ectoderm, impaired migration of the mesoderm, and loss of somites and other structures derived from both the ectoderm and the mesoderm [5].

Associations of Mllt4 with chemical compounds

• PDZ-domain-mediated interaction of the Eph-related receptor tyrosine kinase EphB3 and the ras-binding protein AF6 depends on the kinase activity of the receptor [10].

Physical interactions of Mllt4

• This recruitment was dependent on the C-terminal PDZ domain-binding motif of nectin-1 which is necessary for the binding of afadin, suggesting that nectins recruit S-SCAM through afadin [11].
• The nectin-afadin complex is involved in PDGF-induced cell survival, at least through the PI3K-Akt signaling pathway [12].

Other interactions of Mllt4

• The affinities of PAR-3 and afadin for nectin-1 and -3 were similar [9].
• We have found that the nectin-afadin unit as well as the N-cadherin-catenin unit localizes at the PAs and that both the units cooperatively organize the PAs [11].
• Cystic embryoid bodies derived from afadin(-/-) embryonic stem cells showed normal organization of the endoderm but disorganization of the ectoderm [5].
• It further suggests that the post-translational regulation of Af-6 by Usp9x may be one potential pathway to control the cell adhesion dynamics in mammalian gametogenesis [13].
• Localization of afadin, an adaptor protein of nectin with the actin cytoskeleton, is also nectin-2 dependent at SspJs [14].

Analytical, diagnostic and therapeutic context of Mllt4

• Immunofluorescence and immunoelectron microscopy revealed that LMO7 localized at cell-cell AJs, where afadin localized, in epithelial cells of rat gallbladder [15].

References