Direct interaction between Teashirt and Sex combs reduced proteins, via Tsh's acidic domain, is essential for specifying the identity of the prothorax in Drosophila

teashirt (tsh) encodes a zinc-finger protein that is thought to be part of a network that contributes to regionalization of the Drosophila embryo and establishes the domains of Hox protein function. tsh and the Hox gene Sex combs reduced (Scr) are essential to establish the identity of the first thoracic segment. We used the development of the first thoracic segment as a paradigm for Scr dependent regional morphological distinctions. In this specific context, we asked whether Tsh protein could have a direct influence on Scr activity. Here we present evidence that Tsh interacts directly with Scr and this interaction depends in part on the presence of a short domain located in the N-terminal half of Teashirt called "acidic domain". In vivo, expression of full length Tsh can rescue the tsh null phenotype throughout the trunk whereas Tsh lacking the Scr interacting domain rescues all the trunk defects except in the prothorax. We suggest this provides insights into the mechanism by which Tsh, in concert with Scr, specifies the prothoracic identity.     

Ornithodoros porcinus ticks, bushpigs, and African swine fever in Madagascar

African swine fever (ASF) has recently made its appearance in Madagascar. Ticks of the Ornithodoros moubata group, considered to be O. porcinus Walton, 1962 were formerly known to occur in western Madagascar, but seem to have disappeared from that region. However, three new sites where they occur were found in the humid and cool central highlands of Anatananarivo province. These ticks are known to be efficient reservoirs and vectors of ASF and constitute a considerable complication to the control of the disease. The authors also discuss another potentially complicating factor, the presence of a species of African bushpig, Potamochoerus larvatus.     

Prostaglandin E2-EP4 receptor promotes endothelial cell migration via ERK activation and angiogenesis in vivo

Prostaglandin E2 (PGE(2)), a major product of cyclooxygenase, exerts its functions by binding to four G protein-coupled receptors (EP1-4) and has been implicated in modulating angiogenesis. The present study examined the role of the EP4 receptor in regulating endothelial cell proliferation, migration, and tubulogenesis. Primary pulmonary microvascular endothelial cells were isolated from EP4(flox/flox) mice and were rendered null for the EP4 receptor with adenoCre virus. Whereas treatment with PGE(2) or the EP4 selective agonists PGE(1)-OH and ONO-AE1-329 induced migration, tubulogenesis, ERK activation and cAMP production in control adenovirus-transduced endothelial EP4(flox/flox) cells, no effects were seen in adenoCre-transduced EP4(flox/flox) cells. The EP4 agonist-induced endothelial cell migration was inhibited by ERK, but not PKA inhibitors, defining a functional link between PGE(2)-induced endothelial cell migration and EP4-mediated ERK signaling. Finally, PGE(2), as well as PGE(1)-OH and ONO-AE1-329, also promoted angiogenesis in an in vivo sponge assay providing evidence that the EP4 receptor mediates de novo vascularization in vivo.     

Integrin alpha1beta1 controls reactive oxygen species synthesis by negatively regulating epidermal growth factor receptor-mediated Rac activation

Integrins control many cell functions, including generation of reactive oxygen species (ROS) and regulation of collagen synthesis. Mesangial cells, found in the glomerulus of the kidney, are able to produce large amounts of ROS via the NADPH oxidase. We previously demonstrated that integrin alpha1-null mice develop worse fibrosis than wild-type mice following glomerular injury and this is due, in part, to excessive ROS production by alpha1-null mesangial cells. In the present studies, we describe the mechanism whereby integrin alpha1-null mesangial cells produce excessive ROS. Integrin alpha1-null mesangial cells have constitutively increased basal levels of activated Rac1, which result in its increased translocation to the cell membrane, excessive ROS production, and consequent collagen IV deposition. Basal Rac1 activation is a direct consequence of ligand-independent increased epidermal growth factor receptor (EGFR) phosphorylation in alpha1-null mesangial cells. Thus, our study demonstrates that integrin alpha1beta1-EGFR cross talk is a key step in negatively regulating Rac1 activation, ROS production, and excessive collagen synthesis, which is a hallmark of diseases characterized by irreversible fibrosis.     

Endo180 binds to the C-terminal region of type I collagen

Type I collagen is a fibril-forming heterotrimer composed of two alpha1 and one alpha2 chains and plays a crucial role in cell-matrix adhesion and cell differentiation. Through a comprehensive differential display screening of oncogenic ras target genes, we have shown that the alpha1 chain of type I collagen (col1a1) is markedly down-regulated by the ras oncogene through the mitogen-activated protein kinase pathway. Although ras-transformed cells are no longer able to produce and secrete endogenous collagen, they can still adhere to exogenous collagen, suggesting that the cells express a collagen binding factor(s) on the cell surface. When the region of col1a1 encompassing the C-terminal glycine repeat and C-prodomain (amino acids 1000-1453) was affinity-labeled with human placental alkaline phosphatase, the secreted trimeric fusion protein could bind to the surface of Ras-transformed cells. Using biochemical purification followed by matrix-assisted laser desorption/ionization mass spectrometry analysis, we identified this collagen binding factor as Endo180 (uPARAP, CD280), a member of the mannose receptor family. Ectopic expression of Endo180 in CosE5 cells followed by in situ staining and quantitative binding assays confirmed that Endo180 indeed recognizes and binds to placental alkaline phosphatase. The interaction between Endo180 and the C-terminal region of type I collagen appears to play an important role in cell-matrix adhesion.