Disruption of AKAP-PKA Interaction Induces Hypercontractility With Concomitant Increase in Proliferation Markers in Human Airway Smooth Muscle

With the ability to switch between proliferative and contractile phenotype, airway smooth muscle (ASM) cells can contribute to the progression of airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), in which airway obstruction is associated with ASM hypertrophy and hypercontractility. A-kinase anchoring proteins (AKAPs) have emerged as important regulatory molecules in various tissues, including ASM cells. AKAPs can anchor the regulatory subunits of protein kinase A (PKA), and guide cellular localization via various targeting domains. Here we investigated whether disruption of the AKAP-PKA interaction, by the cell permeable peptide stearated (st)-Ht31, alters human ASM proliferation and contractility. Treatment of human ASM with st-Ht31 enhanced the expression of protein markers associated with cell proliferation in both cultured cells and intact tissue, although this was not accompanied by an increase in cell viability or cell-cycle progression, suggesting that disruption of AKAP-PKA interaction on its own is not sufficient to drive ASM cell proliferation. Strikingly, st-Ht31 enhanced contractile force generation in human ASM tissue with concomitant upregulation of the contractile protein α-sm-actin. This upregulation of α-sm-actin was independent of mRNA stability, transcription or translation, but was dependent on proteasome function, as the proteasome inhibitor MG-132 prevented the st-Ht31 effect. Collectively, the AKAP-PKA interaction appears to regulate markers of the multi-functional capabilities of ASM, and this alter the physiological function, such as contractility, suggesting potential to contribute to the pathophysiology of airway diseases

Epac1 links prostaglandin E2 to β-catenin-dependent transcription during epithelial-to-mesenchymal transition

In epithelial cells, β-catenin is localized at cell-cell junctions where it stabilizes adherens junctions. When these junctions are disrupted, β-catenin can translocate to the nucleus where it functions as a transcriptional cofactor. Recent research has indicated that PGE2 enhances the nuclear function of β-catenin through cyclic AMP. Here, we aim to study the role of the cyclic AMP effector Epac in β-catenin activation by PGE2 in non-small cell lung carcinoma cells.We show that PGE2 induces a down-regulation of E-cadherin, promotes cell migration and enhances β-catenin translocation to the nucleus. This results in β-catenin-dependent gene transcription. We also observed increased expression of Epac1. Inhibition of Epac1 activity using the CE3F4 compound or Epac1 siRNA abolished the effects of PGE2 on β-catenin. Further, we observed that Epac1 and β-catenin associate together. Expression of an Epac1 mutant with a deletion in the nuclear pore localization sequence prevents this association. Furthermore, the scaffold protein Ezrin was shown to be required to link Epac1 to β-catenin.This study indicates a novel role for Epac1 in PGE2-induced EMT and subsequent activation of β-catenin

A taxonomic backbone for the global synthesis of species diversity in the angiosperm order Caryophyllales

The Caryophyllales constitute a major lineage of flowering plants with approximately 12500 species in 39 families. A taxonomic backbone at the genus level is provided that reflects the current state of knowledge and accepts 749 genera for the order. A detailed review of the literature of the past two decades shows that enormous progress has been made in understanding overall phylogenetic relationships in Caryophyllales. The process of re-circumscribing families in order to be monophyletic appears to be largely complete and has led to the recognition of eight new families (Anacampserotaceae, Kewaceae, Limeaceae, Lophiocarpaceae, Macarthuriaceae, Microteaceae, Montiaceae and Talinaceae), while the phylogenetic evaluation of generic concepts is still well underway. As a result of this, the number of genera has increased by more than ten percent in comparison to the last complete treatments in the Families and genera of vascular plants” series. A checklist with all currently accepted genus names in Caryophyllales, as well as nomenclatural references, type names and synonymy is presented. Notes indicate how extensively the respective genera have been studied in a phylogenetic context. The most diverse families at the generic level are Cactaceae and Aizoaceae, but 28 families comprise only one to six genera. This synopsis represents a first step towards the aim of creating a global synthesis of the species diversity in the angiosperm order Caryophyllales integrating the work of numerous specialists around the world