Aberrant expression and localization of connexin43 and connexin30 in a rat glioma cell line

Mennecier, Gregory; Derangeon, Mickaël; Coronas, Valérie; Hervé, Jean-Claude; Mesnil, Marc

doi:10.1002/mc.20393

Cited by 37 publications

(28 citation statements)

References 27 publications

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“…A naturally occurring cytoplasmic C-terminal fragment of Cx43, ~20 kDa in size, has been described and characterized in cultured murine and hamster cells and after Cx43 overexpression in human HeLa cells [7]. Others have also reported Cx43 immunoreactive bands of ~20 kDa, such as in glioma cells [8] and in neonatal rat heart myofibroblasts [9]. A 20-kDa Cx43 immunoreactive band is also clearly detected in zebrafish heart 48 hours postfertilization [10], and the authors also noted an ~30-kDa band in zebrafish ovaries.…”

Section: Resultsmentioning

confidence: 99%

Internal translation of the connexin 43 transcript

et al. 2014

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BackgroundConnexin 43 (Cx43), the most widely expressed gap junction protein, is associated with a number of physiological and pathological conditions. Many functions of Cx43 have been shown to be independent of gap junction formation and only require the expression of Cx43 C-terminal fragments. Recent evidence demonstrated that naturally occurring C-terminal isoforms can be generated via internal translation.FindingsHere, we confirm that C-terminal domains of Cx43, particularly the major 20-kDa isoform, can be independently generated and regulated by internal translation of the same single GJA1 gene transcript that encodes full-length Cx43. Through direct RNA transfection experiments, we provide evidence that internal translation is not due to a bona fide cap-independent IRES-mediated mechanism, as upstream ribosomal scanning or translation is required. In addition to the mTOR pathway, we show for the first time, using both inhibitors and cells from knockout mice, that the Mnk1/2 pathway regulates the translation of the main 20-kDa isoform.ConclusionsInternal translation of the Cx43 transcript occurs but is not cap-independent and requires translation upstream of the internal start codon. In addition to the PI3K/AKT/mTOR pathway, the major 20-kDa isoform is regulated by the Mnk1/2 pathway. Our results have major implications for past and future studies describing gap junction-independent functions of Cx43 in cancer and other pathological conditions. This study provides further clues to the signalling pathways that regulate internal mRNA translation, an emerging mechanism that allows for increased protein diversity and functional complexity from a single mRNA transcript.

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Section: Resultsmentioning

confidence: 99%

Internal translation of the connexin 43 transcript

et al. 2014

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“…Further investigations will be necessary to demonstrate its significance. However, on a fundamental point of view, this work is one of the first ones to report a Cx43 nuclear signal in situ as previous studies only detected it in vitro 10, 26, 27, 28.…”

Section: Discussionmentioning

confidence: 84%

Expression of a gap junction protein, connexin43, in a large panel of human gliomas: new insights

et al. 2016

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Precise diagnosis of low and high grades of brain tumors permits determining therapeutical strategies. So far, diagnosis and prognosis of gliomas were based on histological and genetic criteria which need being completed by a panel of molecular markers. Highly distributed in brain, gap junction proteins, connexins, could be considered as markers of glioma progression as previous studies indicated that expression of a connexin type, connexin43 (Cx43), is inversely correlated to tumor grading. However, this assumption was weakened by the low number of glioma samples used. Taking advantage of tissue microarray technique, we pursued this analysis by studying in situ expression of Cx43 on 85 samples (37 grade IV, 18 grade III, 24 grade II, and 6 grades II to III). Our analysis confirmed the global diminution of Cx43 expression in glioblastomas that was observed in previous studies. However, this analysis brought new insights such as the following ones. First, the high number of samples permitted to show that more than 60% of glioblastomas still express Cx43. Second, no gradual decrease in Cx43 expression was observed between grades II and III, but Cx43 appeared to be a marker distinguishing oligodendrocytic and astrocytic grade III tumors. Third, independently from tumor grade, a Cx43 nuclear staining was detected in areas where leukocytes are present. In conclusion, our study emphasizes the importance of in situ immunohistochemical approaches by giving more precise insights in the subcellular localization of Cx43. It also emphasizes the necessity to carry out such analysis on a wide range of samples to circumvent the high glioma heterogeneity.

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“…GJs are one of the most ubiquitous and ancient forms of intercellular connection involved in signal exchange for the maintenance of homeostasis and cell growth regulation in multicellular organisms (18). Over the past two decades, a number of studies have described a role for GJ intercellular communication in the proliferation and differentiation of numerous types of cells, including SMCs (19).…”

Section: Discussionmentioning

confidence: 99%

Effect of ramipril on the regulation of the expression of connexins 40 and 43 in a rabbit model of arterial balloon injury

Chen

Zhou

et al. 2012

Mol Med Report

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Abstract. Gap junctions (GJs) between the cells play a pivotal role in the transformation and proliferation processes of vascular smooth muscle cells (VSMCs). However, the expression of the component proteins of GJs, connexins 40 and 43 (Cx40 and Cx43), are inconsistent in numerous cases. The aim of this study was to determine whether Cx40 and Cx43 play different roles in the renin-angiotensin system (RAS) involved in the remodeling of GJs in VSMCs under pathological conditions. A total of 28 male New Zealand white rabbits were divided medially into four groups: control, sham injury, injury and injury plus ramipril (0.5 mg/kg/day in the diet for two weeks). The animals were used to set up the rabbit model of arterial balloon injury. Transmission electron microscopy, western blotting, immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) were performed on four samples of ballooned iliac arteries. Larger and more abundant GJs appeared in neointimal VSMCs and there were smaller and fewer GJs following ramipril treatment. mRNA and protein expression levels and level of immunostaining of Cx40 and Cx43 were consistently increased following injury. Although ramipril reduced the change in the levels of Cx43, no significant changes in Cx40 immunostaining, protein or mRNA levels were observed in the ramipril treatments. Ramipril may inhibit neointimal formation and downregulate the expression of Cx43 protein and mRNA, but the drug had no significant effect on the Cx40 protein and mRNA levels, suggesting that it was not Cx40 but Cx43 in GJs that contributes to the process of angiotensin II (Ang II)-converting enzyme inhibitors inhibiting the proliferation of VSMCs in balloon injury.

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Aberrant expression and localization of connexin43 and connexin30 in a rat glioma cell line

Cited by 37 publications

References 27 publications

Internal translation of the connexin 43 transcript

Internal translation of the connexin 43 transcript

Expression of a gap junction protein, connexin43, in a large panel of human gliomas: new insights

Effect of ramipril on the regulation of the expression of connexins 40 and 43 in a rabbit model of arterial balloon injury

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