The cell adhesion gene PVRL3 is associated with congenital ocular defects

Lachke, Salil A.; Higgins, Anne W.; Inagaki, Manabu; Saadi, Irfan; Xi, Qiongchao; Long, Michelle T.; Quade, Bradley J.; Talkowski, Michael E.; Gusella, James F.; Fujimoto, Atsuko; Robinson, Michael L.; Yang, Ying; Duong, Quynh; Shapira, Irit; Motro, Benny; Miyoshi, Jun; Takai, Yoshimi; Morton, Cynthia C.; Maas, Richard L.

doi:10.1007/s00439-011-1064-z

Cited by 48 publications

(47 citation statements)

References 65 publications

(74 reference statements)

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“…Mutations in human PVRL4 (which encodes nectin-4) that result in the failure of nectin-4 binding to nectin-1 cause an ectodermal dysplasiasyndactyly syndrome that is characterized by the combination of hair and tooth abnormalities, alopecia and cutaneous syndactyly (Brancati et al, 2010). Recent genome-wide association studies of various populations, including Japanese and African Americans, have shown a genetic association between singlenucleotide polymorphisms (SNPs) in PVRL2 (which encodes nectin-2) and late-onset alzheimer's disease (Harold et al, 2009;Logue et al, 2011;Takei et al, 2009), and mutations in PVRL3 (which encodes nectin-3) are associated with human ocular disease and congenital ocular defects (Lachke et al, 2012).…”

Section: Nectins In Human Diseasesmentioning

confidence: 99%

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

Rikitake

Mandai

Takai

2012

Journal of Cell Science

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138

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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.

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Section: Nectins In Human Diseasesmentioning

confidence: 99%

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

Rikitake

Mandai

Takai

2012

Journal of Cell Science

Self Cite

138

121

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“…6.9b; Lachke et al 2012). On the other hand, E-and N-cadherins are expressed in the developing mouse lens (Cain et al 2008;Lachke et al 2012;Maddala et al 2011), where E-cadherin is localized at the cell-cell junction of the lens epithelial cells (Lachke et al 2012), and N-cadherin at the cell-cell junction of the fiber cells ( Fig. 6.9b; Maddala et al 2011).…”

Section: Heterotypic Adhesion: Formation Of Lensmentioning

confidence: 97%

“…F-actin is not depicted (Chow and Lang 2001;McAvoy 1980). All four nectin genes, Pvrl1, Pvrl2, Pvrl3, and Pvrl4 are expressed in the developing mouse lens (Lachke et al 2012;Okabe et al 2004a). Among them, nectin-1 is localized at the cell surface of the fiber cells adjacent to the lens epithelial cells (Lachke et al 2012;Maddala et al 2011), nectin-2 is distributed in both the lens epithelial and fiber cells (Okabe et al 2004a), and nectin-3 is localized at the apical surface of the lens epithelial cells, which face the fiber cells ( Fig.…”

Section: Heterotypic Adhesion: Formation Of Lensmentioning

confidence: 99%

“…Among them, nectin-1 is localized at the cell surface of the fiber cells adjacent to the lens epithelial cells (Lachke et al 2012;Maddala et al 2011), nectin-2 is distributed in both the lens epithelial and fiber cells (Okabe et al 2004a), and nectin-3 is localized at the apical surface of the lens epithelial cells, which face the fiber cells ( Fig. 6.9b; Lachke et al 2012). On the other hand, E-and N-cadherins are expressed in the developing mouse lens (Cain et al 2008;Lachke et al 2012;Maddala et al 2011), where E-cadherin is localized at the cell-cell junction of the lens epithelial cells (Lachke et al 2012), and N-cadherin at the cell-cell junction of the fiber cells ( Fig.…”

Section: Heterotypic Adhesion: Formation Of Lensmentioning

confidence: 99%

“…6.9b; Maddala et al 2011). In the nectin-3-knockout lens, small slit-like separations in the fiber cells adjacent to the lens epithelial cells are observed (Lachke et al 2012), suggesting that the trans-interactions of nectin-1 and -3 and nectin-2 and -3 between the lens epithelial and fiber cells are crucial for lens development.…”

Section: Heterotypic Adhesion: Formation Of Lensmentioning

confidence: 99%

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Cooperative Roles of Nectins with Cadherins in Physiological and Pathological Processes

Fujiwara

Mizoguchi

Takai

2016

The Cadherin Superfamily

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Mammalian tissues and organs are composed of cells of different types and these cells adhere to one another to form societies of cells including the mesenchyme and the epithelium. Cell-cell adhesion in the mesenchyme is weak whereas cells are organized into closely adherent barrier-forming sheets by cellcell adhesions in the epithelium. Cell-cell adhesion is organized to allow the release or incorporation of individual cells during various physiological or pathological processes, for example, organ development and growth, maintenance and repair of tissues, or tumorigenesis. One prominent cell-cell adhesion apparatus is adherens junctions (AJs). The central structural components of AJs are transmembrane cellcell adhesion molecules, cadherins and nectins. Nectins recruit cadherins to the cell-cell contact sites and mediate cell-cell adhesions that control local membrane dynamics for cell polarization and coordinate shape change at the cellular level. Nectins are engaged in calcium-independent homophilic and heterophilic transinteractions between opposing cells in numerous tissues and cell types to form homotypic and heterotypic cell-cell adhesion, whereas cadherins are primarily involved in calcium-dependent homophilic trans-interactions between opposing cells to form homotypic cell-cell adhesion. Nectins function cooperatively with or independently of cadherins to control physiological processes and cooperative ones include the formation of AJs and apico-basal polarity, apical constriction, contact inhibition of cell movement and proliferation, formation of synapse, formation of checkerboard-like cell arrangement, ciliary epithelium and lens, and

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Exome sequencing provides additional evidence for the involvement of ARHGAP29 in Mendelian orofacial clefting and extends the phenotypic spectrum to isolated cleft palate

Liu

Busch

Eliason³

et al. 2017

Birth Defects Research

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Background Recent advances in genomics methodologies, in particular the availability of next-generation sequencing approaches have made it possible to identify risk loci throughout the genome, in particular the exome. In the current study, we present findings from an exome study conducted in five affected individuals of a multiplex family with cleft palate only (CPO). Methods The GEnomeMINIng (GEMINI) pipeline was used to functionally annotate the SNPs, insertions and deletions (In/Del). Filtering methods were applied to identify variants that are clinically relevant and present in affected individuals at minor allele frequencies (≤1%) in the 1000 Genomes Project, Single Nucleotide Polymorphism (dbSNP), Exome Aggregation Consortium (ExAC), and Exome Variant Server (EVS) databases. The bioinformatics tool Systems Tool for Craniofacial Expression-based Gene Discovery (SysFACE) was used to prioritize cleft candidates in our list of variants, and Sanger sequencing was used to validate the presence of identified variants in affected and unaffected relatives. Results Our analyses approach narrowed the candidates down to the novel missense variant in ARHGAP29 (GenBank: NM_004815.3, NP_004806.3;c.1654T>C [p.Ser552Pro]. A functional assay in zebrafish embryos showed that the encoded protein lacks the activity possessed by its wild-type (WT) counterpart, and migration assays revealed that keratinocytes transfected with WT ARHGAP29 migrated faster than counterparts transfected with the p.Ser552Pro ARHGAP29 variant or empty vector (control). Conclusions These findings reveals ARHGAP29 to be a regulatory protein essential for proper development of the face, identifies an amino-acid that is key for this, and provides a potential new diagnostic tool.

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The cell adhesion gene PVRL3 is associated with congenital ocular defects

Cited by 48 publications

References 65 publications

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

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

Cooperative Roles of Nectins with Cadherins in Physiological and Pathological Processes

Exome sequencing provides additional evidence for the involvement of ARHGAP29 in Mendelian orofacial clefting and extends the phenotypic spectrum to isolated cleft palate

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