The adhering junctions of valvular interstitial cells: molecular composition in fetal and adult hearts and the comings and goings of plakophilin-2 in situ, in cell culture and upon re-association with scaffolds

Barth, Mareike; Rickelt, Steffen; Noffz, Edeltraut; Winter-Simanowski, Stefanie; Niemann, Heiner; Akhyari, Payam; Lichtenberg, Artur; Franke, Werner W.

doi:10.1007/s00441-011-1315-2

Cited by 11 publications

(8 citation statements)

References 91 publications

(88 reference statements)

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“…PKP2 specifically interacts with EGFR via its N‐terminal head domain and then enhance EGFR autophosphorylation, promoting the activation of EGFR‐mediated signaling pathways . An additional report has found that PKP2 is functionally associated with E‐cadherin and involved in β‐catenin‐mediated signaling pathways which are markers of epithelial‐mesenchymal transition (EMT) . The function of EMT is to reduce cell–cell adhesion and increase the motility of tumor cells .…”

Section: Discussionmentioning

confidence: 99%

Up‐regulation of plakophilin‐2 is correlated with the progression of glioma

et al. 2017

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Glioma is the most common type of primary brain tumor in the CNS. Due to its poor prognosis and high mortality rates, it is urgent to find out more effective therapies. Plakophilin-2 (PKP2) is a widespread desmosomal plaque protein. Recently, the important roles of PKP2 in the proliferation and migration of cancer cells and tumor progression has been shown. However, the expression and potential function of PKP2 in glioma was still unclear. In this study, we demonstrated that PKP2 protein expression level was increased in glioma tissues compared with normal brain tissues, and its level was significantly associated with the Ki-67 expression and WHO grade by Western blot analysis and immunohistochemistry. Clinically, high PKP2 expression was tightly related to poor prognosis of glioma patients. Interestingly, we found that down-regulated PKP2 expression was shown to inhibit the migration of cells in glioma. Moreover, cell counting kit (CCK)-8 and colony formation analyses proved that reduced expression of PKP2 could weaken glioma cell proliferation. Taken together, these data uncover a potential role for PKP2 in the pathogenic process of glioma, suggesting that PKP2 may be a promising therapeutic target of glioma.

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Section: Discussionmentioning

confidence: 99%

Up‐regulation of plakophilin‐2 is correlated with the progression of glioma

et al. 2017

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“…Most notably, one of the top associated genes in human patients, GRIK2 , encodes a glutamate receptor recruited to the synaptic membrane by CDH2/catenin complexes [47] and another top candidate, PKP2 , mediates CDH2 cell adhesion and desmosomal junctions [48]. In addition, several genes whose expression levels correlate with the top human OCD-associated SNPs interact with the genes we identify in dogs: LRSAM1 (cerebellum) and NARS (frontal lobe) interact with ATXN1; SPAG9 (cerebellum) acts in developmental pathways with CDH2 and CTNNA2 [49].…”

Section: Discussionmentioning

confidence: 99%

Candidate genes and functional noncoding variants identified in a canine model of obsessive-compulsive disorder

et al. 2014

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BackgroundObsessive-compulsive disorder (OCD), a severe mental disease manifested in time-consuming repetition of behaviors, affects 1 to 3% of the human population. While highly heritable, complex genetics has hampered attempts to elucidate OCD etiology. Dogs suffer from naturally occurring compulsive disorders that closely model human OCD, manifested as an excessive repetition of normal canine behaviors that only partially responds to drug therapy. The limited diversity within dog breeds makes identifying underlying genetic factors easier.ResultsWe use genome-wide association of 87 Doberman Pinscher cases and 63 controls to identify genomic loci associated with OCD and sequence these regions in 8 affected dogs from high-risk breeds and 8 breed-matched controls. We find 119 variants in evolutionarily conserved sites that are specific to dogs with OCD. These case-only variants are significantly more common in high OCD risk breeds compared to breeds with no known psychiatric problems. Four genes, all with synaptic function, have the most case-only variation: neuronal cadherin (CDH2), catenin alpha2 (CTNNA2), ataxin-1 (ATXN1), and plasma glutamate carboxypeptidase (PGCP). In the 2 Mb gene desert between the cadherin genes CDH2 and DSC3, we find two different variants found only in dogs with OCD that disrupt the same highly conserved regulatory element. These variants cause significant changes in gene expression in a human neuroblastoma cell line, likely due to disrupted transcription factor binding.ConclusionsThe limited genetic diversity of dog breeds facilitates identification of genes, functional variants and regulatory pathways underlying complex psychiatric disorders that are mechanistically similar in dogs and humans.

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“…On the other hand, in this context, we do not forget to mention the specific occurrences of individual desmosomal molecules in other ensembles such as desmoplakin in the complexus adhaerentes of parts of lymphatic endothelia (Schmelz and Franke 1993; Hämmerling et al 2006; Moll et al 2009), plakophilin Pkp-2 in AJs of certain very proliferative stages of mesenchymal cells (e.g., Barth et al 2009, 2012; Rickelt et al 2010; Rickelt 2012) and the “free” Dsg-2 glycoproteins dispersed on the surfaces of certain types of melanoma cells (Schmitt et al 2007; Rickelt et al 2008). Particularly complex “hybrid junctions” are the composite junctions ( areae compositae ) connecting mammalian cardiomyocytes (Franke et al 2006) and the “meningioma junctions” in which E- or N-cadherin can be associated not only with α- and β-catenin, plakoglobin and protein p120 but also with the “desmosomal protein”, plakophilin Pkp-2 (Akat et al 2008).…”

Section: Discussionmentioning

confidence: 99%

The cell–cell junctions of mammalian testes: I. The adhering junctions of the seminiferous epithelium represent special differentiation structures

et al. 2014

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The seminiferous tubules and the excurrent ducts of the mammalian testis are physiologically separated from the mesenchymal tissues and the blood and lymph system by a special structural barrier to paracellular translocations of molecules and particles: the “blood–testis barrier”, formed by junctions connecting Sertoli cells with each other and with spermatogonial cells. In combined biochemical as well as light and electron microscopical studies we systematically determine the molecules located in the adhering junctions of adult mammalian (human, bovine, porcine, murine, i.e., rat and mouse) testis. We show that the seminiferous epithelium does not contain desmosomes, or “desmosome-like” junctions, nor any of the desmosome-specific marker molecules and that the adhering junctions of tubules and ductules are fundamentally different. While the ductules contain classical epithelial cell layers with E-cadherin-based adherens junctions (AJs) and typical desmosomes, the Sertoli cells of the tubules lack desmosomes and “desmosome-like” junctions but are connected by morphologically different forms of AJs. These junctions are based on N-cadherin anchored in cytoplasmic plaques, which in some subforms appear thick and dense but in other subforms contain only scarce and loosely arranged plaque structures formed by α- and β-catenin, proteins p120, p0071 and plakoglobin, together with a member of the striatin family and also, in rodents, the proteins ZO-1 and myozap. These N-cadherin-based AJs also include two novel types of junctions: the “areae adhaerentes”, i.e., variously-sized, often very large cell-cell contacts and small sieve-plate-like AJs perforated by cytoplasm-to-cytoplasm channels of 5–7 nm internal diameter (“cribelliform junctions”). We emphasize the unique character of this epithelium that totally lacks major epithelial marker molecules and structures such as keratin filaments and desmosomal elements as well as EpCAM- and PERP-containing junctions. We also discuss the nature, development and possible functions of these junctions.Electronic supplementary materialThe online version of this article (doi:10.1007/s00441-014-1906-9) contains supplementary material, which is available to authorized users.

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The adhering junctions of valvular interstitial cells: molecular composition in fetal and adult hearts and the comings and goings of plakophilin-2 in situ, in cell culture and upon re-association with scaffolds

Cited by 11 publications

References 91 publications

Up‐regulation of plakophilin‐2 is correlated with the progression of glioma

Up‐regulation of plakophilin‐2 is correlated with the progression of glioma

Candidate genes and functional noncoding variants identified in a canine model of obsessive-compulsive disorder

The cell–cell junctions of mammalian testes: I. The adhering junctions of the seminiferous epithelium represent special differentiation structures

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