title: Requirement of interaction of nectin-1alpha/HveC with afadin for efficient cell-cell spread of herpes simplex virus type 1.
abstract: We recently found a novel cell-cell adhesion system at cadherin-based adherens junctions (AJs), consisting at least of nectin, a Ca(2+)-independent homophilic immunoglobulin-like adhesion molecule, and afadin, an actin filament-binding protein that connects nectin to the actin cytoskeleton. Nectin is associated with cadherin through afadin and alpha-catenin. The cadherin-catenin system increases the concentration of nectin at AJs in an afadin-dependent manner. Nectin constitutes a family consisting of three members: nectin-1, -2, and -3. Nectin-1 serves as an entry and cell-cell spread mediator of herpes simplex virus type 1 (HSV-1). We studied here a role of the interaction of nectin-1alpha with afadin in entry and/or cell-cell spread of HSV-1. By the use of cadherin-deficient L cells overexpressing the full length of nectin-1alpha capable of interacting with afadin and L cells overexpressing a truncated form of nectin-1alpha incapable of interacting with afadin, we found that the interaction of nectin-1alpha with afadin increased the efficiency of cell-cell spread, but not entry, of HSV-1. This interaction did not affect the binding to nectin-1alpha of glycoprotein D, a viral component mediating entry of HSV-1 into host cells. Furthermore, the cadherin-catenin system increased the efficiency of cell-cell spread of HSV-1, although it also increased the efficiency of entry of HSV-1. It is likely that efficient cell-cell spread of HSV-1 is caused by afadin-dependent concentrated localization of nectin-1alpha at cadherin-based AJs.
authors: Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.
authors: T
authors: T
authors: Sakisaka
authors: T
authors: T
authors: Taniguchi
authors: H
authors: H
authors: Nakanishi
authors: K
authors: K
authors: Takahashi
authors: M
authors: M
authors: Miyahara
authors: W
authors: W
authors: Ikeda
authors: S
authors: S
authors: Yokoyama
authors: Y F
authors: YF
authors: Peng
authors: K
authors: K
authors: Yamanishi
authors: Y
authors: Y
authors: Takai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D016547:Kinesins; D007739:L Cells; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009218:Myosins; D000075983:Nectins; D014759:Viral Envelope Proteins / Q000378:metabolism
chemical_list: C095516:AFDN protein, human; C490657:Afdn protein, mouse; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C000619010:NECTIN1 protein, human; C000619015:Nectin1 protein, mouse; D000075983:Nectins; D014759:Viral Envelope Proteins; C108835:afadin; C039447:glycoprotein D, Human herpesvirus 1; D009218:Myosins; D016547:Kinesins