A 14-3-3γ dimer-based scaffold bridges CtBP1-S/BARS to PI(4)KIIIβ to regulate post-Golgi carrier formation

Valente, Carmen; Turacchio, Gabriele; Mariggiò, Stefania; Pagliuso, Alessandro; Gaibisso, Renato; Tullio, Giuseppe Di; Santoro, Michele; Formiggini, Fabio; Spanò, Stefania; Piccini, Daniele; Polishchuk, Roman; Colanzi, Antonino; Luini, Alberto; Corda, Daniela

doi:10.1038/ncb2445

Cited by 77 publications

(133 citation statements)

References 70 publications

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“…Our results indicate that 14-3-3c regulates desmosome formation in multiple cell types, as loss of 14-3-3c in HCT116 cells, which are derived from the colon, and in the seminiferous epithelium leads to a decrease in cell-cell adhesion and in desmosome formation. Our results are also consistent with the previously reported role of 14-3-3c in the transport of proteins from the Golgi complex to the cell border (Valente et al, 2012). One reason for the differences in these results and those reported by Steinacker and colleagues (Steinacker et al, 2005) could be that another 14-3-3 family member binds to plakoglobin and stimulates desmosome formation in the 14-3-3c 2/2 mice, and that this compensation is not observed upon shRNA-mediated knockdown in the testis.…”

Section: Discussionsupporting

confidence: 82%

“…This is consistent with previous observations that showed that PKCm localizes to the Golgi complex (Hausser et al, 2002;Prestle et al, 1996) and is required for the fission of vesicles carrying cargo to the cell border (Liljedahl et al, 2001). A 14-3-3c dimer is required for carrier formation at the Golgi complex along with PKCm (Valente et al, 2012), suggesting that the loss of 14-3-3c could disrupt desmosome formation owing to defects in plakoglobin transport.…”

Section: Discussionsupporting

confidence: 81%

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14-3-3γ meditated transport of plakoglobin to the cell border is required for the initiation of desmosome assembly in vitro and in vivo

Sehgal

Mukhopadhyay

Rajan

et al. 2014

Journal of Cell Science

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The regulation of cell-cell adhesion is important for the processes of tissue formation and morphogenesis. Here we report that loss of 14-3-3γ leads to a decrease in cell-cell adhesion and a defect in the transport of plakoglobin (PG) and other desmosomal proteins to the cell border in HCT116 cells and in the mouse testis. 14-3-3γ binds to PG in a PKCμ dependent fashion resulting in microtubule dependent transport of PG to the border. Transport of PG to the border is dependent on the KIF5B/KLC1 complex. Knockdown of KIF5B in HCT116 cells or in the mouse testis, results in a phenotype similar to that observed with 14-3-3γ knockdown. Our results suggest that loss of 14-3-3γ leads to decreased desmosome formation and a decrease in cell-cell adhesion in vitro and in vivo in the mouse testis leading to defects in testis organization and spermatogenesis.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 81%

14-3-3γ meditated transport of plakoglobin to the cell border is required for the initiation of desmosome assembly in vitro and in vivo

Sehgal

Mukhopadhyay

Rajan

et al. 2014

Journal of Cell Science

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“…This method allows the determination of protein-protein interactions indicated by an apparent molecular proximity below 10 nm (Eiseler et al, 2012(Eiseler et al, , 2016Gu et al, 2004;Kunkel and Newton, 2009;Oser et al, 2010;Valente et al, 2012;Wille et al, 2014;Wouters et al, 1998;Zeug et al, 2012). The FRET acceptor in a region of interest (ROI) was bleached by an intensive laser line and increase in donor fluorescence, indicating FRET, was measured.…”

Section: Intestinal Permeability Assaymentioning

confidence: 99%

Cortactin is a scaffolding platform for the E-Cadherin adhesion complex controlled by protein kinase D1 phosphorylation

Sroka

Lint

Katz

et al. 2016

Journal of Cell Science

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Dynamic regulation of cell-cell adhesion by the coordinated formation and dissolution of E-cadherin-based adherens junctions is crucial for tissue homeostasis. The actin-binding protein cortactin interacts with E-cadherin and enables F-actin accumulation at adherens junctions. Here, we were interested to study the broader functional interactions of cortactin in adhesion complexes. In line with literature, we demonstrate that cortactin binds to E-cadherin, and that a posttranslational modification of cortactin, RhoA-induced phosphorylation by protein kinase D1 (PKD1; also known as PRKD1) at S298, impairs adherens junction assembly and supports their dissolution. Two new S298-phosphorylation-dependent interactions were also identified, namely, that phosphorylation of cortactin decreases its interaction with β-catenin and the actin-binding protein vinculin. In addition, binding of vinculin to β-catenin, as well as linkage of vinculin to F-actin, are also significantly compromised upon phosphorylation of cortactin. Accordingly, we found that regulation of cell-cell adhesion by phosphorylation of cortactin downstream of RhoA and PKD1 is vitally dependent on vinculin-mediated protein interactions. Thus, cortactin, unexpectedly, is an important integration node for the dynamic regulation of protein complexes during breakdown and formation of adherens junctions.

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“…Native 14-3-3 exists in monomeric and dimeric states as homo-and heterodimers, respectively, although 14-3-3g is almost entirely dimeric. 57 Glu15 is part of a triad of residues (Leu13, Ala14, and Glu15) necessary for 14-3-3g dimerization, 58,59 and its ability to complex with other proteins is potentially inhibited by substitution at this site.…”

mentioning

confidence: 99%

De Novo Mutations in YWHAG Cause Early-Onset Epilepsy

Guella

McKenzie

Evans

et al. 2017

The American Journal of Human Genetics

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Massively parallel sequencing has revealed many de novo mutations in the etiology of developmental and epileptic encephalopathies (EEs), highlighting their genetic heterogeneity. Additional candidate genes have been prioritized in silico by their co-expression in the brain. Here, we evaluate rare coding variability in 20 candidates nominated with the use of a reference gene set of 51 established EE-associated genes. Variants within the 20 candidate genes were extracted from exome-sequencing data of 42 subjects with EE and no previous genetic diagnosis. We identified 7 rare non-synonymous variants in 7 of 20 genes and performed Sanger sequence validation in affected probands and parental samples. De novo variants were found only in SLC1A2 (aka EAAT2 or GLT1) (c.244G>A [p.Gly82Arg]) and YWHAG (aka 14-3-3g) (c.394C>T [p.Arg132Cys]), highlighting the potential cause of EE in 5% (2/42) of subjects. Seven additional subjects with de novo variants in SLC1A2 (n ¼ 1) and YWHAG (n ¼ 6) were subsequently identified through online tools. We identified a highly significant enrichment of de novo variants in YWHAG, establishing their role in early-onset epilepsy, and we provide additional support for the prior assignment of SLC1A2. Hence, in silico modeling of brain co-expression is an efficient method for nominating EE-associated genes to further elucidate the disorder's etiology and genotype-phenotype correlations.

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A 14-3-3γ dimer-based scaffold bridges CtBP1-S/BARS to PI(4)KIIIβ to regulate post-Golgi carrier formation

Cited by 77 publications

References 70 publications

14-3-3γ meditated transport of plakoglobin to the cell border is required for the initiation of desmosome assembly in vitro and in vivo

14-3-3γ meditated transport of plakoglobin to the cell border is required for the initiation of desmosome assembly in vitro and in vivo

Cortactin is a scaffolding platform for the E-Cadherin adhesion complex controlled by protein kinase D1 phosphorylation

De Novo Mutations in YWHAG Cause Early-Onset Epilepsy

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