Nectin and junctional adhesion molecule are critical cell adhesion molecules for the apico‐basal alignment of adherens and tight junctions in epithelial cells

Yamada, Tomohiro; Kuramitsu, Kaori; Rikitsu, Etsuko; Kurita, Souichi; Ikeda, Wataru; Takai, Yoshimi

doi:10.1111/gtc.12091

Cited by 12 publications

(9 citation statements)

References 49 publications

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“…It has been localized both to tight [88] and adherens [89] junctions by immuno-EM: its distribution likely overlaps both junctions. Afadin interacts with JAM-A [73] and with elements of the polarity complex; these proteins together with nectin and ZO-1 appear to be required for the proper apical positioning of the tight junction relative to the adherens junction [90]. Afadin can interact with ZO-1 when tight junctions are disrupted as after calcium removal, but this interaction is not detectable in polarized cells [91].…”

Section: Core Components Of the Tight Junction: Integral Membrane mentioning

confidence: 99%

Architecture of tight junctions and principles of molecular composition

Itallie¹,

Anderson²

2014

Seminars in Cell & Developmental Biology

439

349

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The tight junction creates an intercellular barrier limiting paracellular movement of solutes and material across epithelia. Currently many proteins have been identified as components of the tight junction and understanding their architectural organization and interactions is critical to understanding the biology of the barrier. In general the architecture can be conceptualized into compartments with the transmembrane barrier proteins (claudins, occludin, JAM-A, etc.), linked to peripheral scaffolding proteins (such as ZO-1, afadin, MAGI1, etc.) which are in turned linked to actin and microtubules through numerous linkers (cingulin, myosins, protein 4.1, etc.). Within this complex network are associated many signaling proteins that affect the barrier and broader cell functions. The PDZ domain is a commonly used motif to specifically link individual junction protein pairs. Here we review some of the key proteins defining the tight junction and general themes of their organization with the perspective that much will be learned about function by characterizing the detailed architecture and subcompartments within the junction.

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Section: Core Components Of the Tight Junction: Integral Membrane mentioning

confidence: 99%

Architecture of tight junctions and principles of molecular composition

Itallie¹,

Anderson²

2014

Seminars in Cell & Developmental Biology

439

349

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“…2d ). PVRL1, also known as nectin1, was first identified as an afadin-binding protein and serves as a cell adhesion molecule at AJs 27 . However, the formation of TJs in BMECs generally requires the existence of AJs.…”

Section: Discussionmentioning

confidence: 99%

miR-1303 regulates BBB permeability and promotes CNS lesions following CA16 infections by directly targeting MMP9

Huang

et al. 2018

Emerging Microbes & Infections

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Coxsackievirus A16 (CA16) is a member of the Picornaviridae family and causes mild and self-limiting hand, foot, and mouth disease (HFMD) in infants and young children. CA16 infection can also progress to central nervous system (CNS) complications; however, the underlying mechanism by which CA16 penetrates the blood-brain barrier (BBB) and then causes CNS damage remains unclear. This study aimed to explore the mechanism of CA16 neurotropic tropism by establishing an in vitro BBB model with CA16 infection and an in vivo CA16 rhesus monkey infant infection model. The results showed that CA16 infection induced increased permeability of the BBB accompanied by upregulation of matrix metalloproteinase 9 (MMP9) expression. Subsequently, high-throughput miRNA sequencing technology and bioinformatics analysis revealed that miR-1303 may regulate BBB permeability by targeting MMP9. Next, we used dual-luciferase, qRT-PCR, and western blot assays to provide evidence of MMP9 targeting by miR-1303. Further experiments revealed that CA16 infection promoted the degradation of junctional complexes (Claudin4, Claudin5, VE-Cadherin, and ZO-1), likely by downregulating miR-1303 and upregulating MMP9. Finally, EGFP-CA16 infection could enter the CNS by facilitating the degradation of junctional complexes, eventually causing neuroinflammation and injury to the CNS, which was confirmed using the in vivo rhesus monkey model. Our results indicate that CA16 might penetrate the BBB and then enter the CNS by downregulating miR-1303, which disrupts junctional complexes by directly regulating MMP9 and ultimately causing pathological CNS changes. These results provide new therapeutic targets in HFMD patients following CA16 infection.

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“…9 This result is unusual, as nectin-3 is understood to predominantly localize to the adherens junction, where it mediates adhesion and provides the stimulating signals to initiate tight junction formation. 29,45 Thus far, there have been no reports involving nectin-3 in the regulation of paracellular permeability as is well documented for claudins 46 and occludin, 47 key facilitators of this function in the tight junction. 48 Therefore, it may be that the localization of nectin-3 to the cellular junctions may represent a compensatory mechanism to maintain adhesion and retain some epithelial barrier integrity given the loss of the adherens junction and desmosomes in UECs at this time.…”

Section: Discussionmentioning

confidence: 99%

Nectin-3 Is Increased in the Cell Junctions of the Uterine Epithelium at Implantation

Poon¹,

Madawala²,

Dowland

et al. 2016

Reprod. Sci.

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Uterine luminal epithelial cells (UECs) undergo the plasma membrane transformation in the transition to receptivity. This involves transient alterations in the apical junctional complex (AJC) including increases to the depth and complexity of the tight junction, loss of the adherens junction, and a decrease in the number of desmosomes along the lateral cell membranes. Nectin-3 is key protein involved in the structure and function of the AJC. This study, used immunofluorescence, Western blotting, colocalization, and coimmunoprecipitation analyses, to investigate whether nectin-3 was present in the rat uterus and was regulated by hormones and the blastocyst during early pregnancy. The results showed that nectin-3 was present in UECs as 3 molecular weight protein isoforms (80 kDa, 60 kDa, and 32 kDa). At the time of fertilization (day 1 of pregnancy), nectin-3 was localized basally, but at the time of implantation, (day 6 of pregnancy) when UECs were receptive, nectin-3 increased in the cellular junctions. When UECs returned to the nonreceptive state (day 9 of pregnancy), nectin-3 redistributed back to the cell cytoplasm. This study also showed that nectin-3 localization at the cell junctions was likely to be controlled by progesterone; however, neither ovarian hormones nor the blastocyst regulated protein abundance. This study further showed that while nectin-3 localized to the tight junction at the time of implantation, it did not interact with occludin or l-afadin. These results suggest that at the time of implantation, nectin-3 may contribute to the formation of the tight junction in a protein complex independent from occludin and l-afadin.

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Nectin and junctional adhesion molecule are critical cell adhesion molecules for the apico‐basal alignment of adherens and tight junctions in epithelial cells

Cited by 12 publications

References 49 publications

Architecture of tight junctions and principles of molecular composition

Architecture of tight junctions and principles of molecular composition

miR-1303 regulates BBB permeability and promotes CNS lesions following CA16 infections by directly targeting MMP9

Nectin-3 Is Increased in the Cell Junctions of the Uterine Epithelium at Implantation

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