Neurospora crassa FKBP22 is a novel ER chaperone and functionally cooperates with BiP

FK506 binding proteins (FKBPs) belong to the family of peptidyl prolyl cis-trans isomerases (PPIases) catalyzing the cis/trans isomerisation of Xaa-Pro bonds in oligopeptides and proteins. FKBPs are involved in folding, assembly and trafficking of proteins. However, only limited knowledge is available about the roles of FKBPs in the endoplasmic reticulum (ER) and their interaction with other proteins. Here we show the ER located Neurospora crassa FKBP22 to be a dimeric protein with PPIase and a novel chaperone activity. While the homodimerization of FKBP22 is mediated by its carboxy-terminal domain, the amino-terminal domain is a functional FKBP domain. The chaperone activity is mediated by the FKBP domain but is exhibited only by the full-length protein. We further demonstrate a direct interaction between FKBP22 and BiP, the major Hsp70 chaperone in the ER. The binding to BiP is mediated by the FKBP domain of FKBP22. Interestingly BiP enhances the chaperone activity of FKBP22. Both proteins form a stable complex with an unfolded substrate protein and thereby prevent its aggregation. These results suggest that BiP and FKBP22 form a folding helper complex with a high chaperoning capacity in the ER of Neurospora crassa.     

Tropheryma whipplei in the Environment: Survey of Sewage Plant Influxes and Sewage Plant Workers

We studied the prevalence of Tropheryma whipplei in influxes to 46 sewage treatment plants and in stool, mouthwash fluids, and dental plaques of 64 healthy workers in those facilities and 146 disease control patients. T. whipplei was found in sewage water, in stool of healthy individuals, and significantly more often in stool of workers exposed to sewage water.     

Sphingosine 1-phosphate phosphatase 2 is induced during inflammatory responses

Sphingosine 1-phosphate (S1P) levels in cells and, consequently, its bioactivity as a signalling molecule are controlled by the action of enzymes responsible for its synthesis and degradation. In the present report, we examined alterations in expression patterns of enzymes involved in S1P-metabolism (sphingosine kinases including their splice variants, sphingosine 1-phosphate phosphatases, and sphingosine 1-phosphate lyase) under certain inflammatory conditions. We found that sphingosine kinase type 1 (SPHK1) mRNA could be triggered in a cell type-specific manner; individual SPHK1 splice variants were induced with similar kinetics. Remarkably, expression and activity of S1P phosphatase 2 (SPP2) was found to be highly upregulated by inflammatory stimuli in a variety of cells (e.g., neutrophils, endothelial cells). Bandshift analysis using oligonucleotides spanning predicted NFkappaB sites within the SPP2 promoter and silencing of NFkappaB/RelA via RelA-directed siRNA demonstrated that SPP2 is an NFkappaB-dependent gene. Silencing of SPP2 expression in endothelial cells, in turn, led to a marked reduction of TNF-alpha-induced IL-1beta mRNA and protein and to a partial reduction of induced IL-8, suggesting a pro-inflammatory role of SPP2. Notably, up-regulation of SPP2 was detected in samples of lesional skin of patients with psoriasis, an inflammatory skin disease. This study provides detailed insights into the regulation of SPP2 gene expression and suggests that SPP2 might be a novel player in pro-inflammatory signalling.     

Evolution of <Emphasis Type="Italic">Hox3</Emphasis> and <Emphasis Type="Italic">ftz</Emphasis> in arthropods: insights from the crustacean <Emphasis Type="Italic">Daphnia pulex</Emphasis>

The Drosophila melanogaster genes zerknüllt (zen) and fushi tarazu (ftz) are members of the Hox gene family whose roles have changed significantly in the insect lineage and thus provide an opportunity to study the mechanisms underlying the functional evolution of Hox proteins. We have studied the expression of orthologs of zen (DpuHox3) and ftz (Dpuftz) in the crustacean Daphnia pulex (Branchiopoda), both of which show a dynamic expression pattern. DpuHox3 is expressed in a complex pattern in early embryogenesis, with the most anterior boundary of expression lying at the anterior limit of the second antennal segment as well as a ring of expression around the embryo. In later embryos, DpuHox3 expression is restricted to the mesoderm of mandibular limb buds. Dpuftz is first expressed in a ring around the embryo following the posterior limit of the mandibular segment. Later, Dpuftz is restricted to the posterior part of the mandibular segment. This is the first report of expression of a Hox3 ortholog in a crustacean, and together with Dpuftz data, the results presented here show that Hox3 and ftz have retained a Hox-like expression pattern in crustaceans. This is in accordance with the proposed model of Hox3 and ftz evolution in arthropods and allows a more precise pinpointing of the loss of ftz “Hox-like behaviour”: in the lineage between the Branchiopoda and the basal insect Thysanura.     

Diversification in the Andes: age and origins of South American Heliotropium lineages (Heliotropiaceae, Boraginales)

The uplift of the Andes was a major factor for plant diversification in South America and had significant effects on the climatic patterns at the continental scale. It was crucial for the formation of the arid environments in south-eastern and western South America. However, both the timing of the major stages of the Andean uplift and the onset of aridity in western South America remain controversial. In this paper we examine the hypothesis that the Andean South American groups of Heliotropium originated and diversified in response to Andean orogeny during the late Miocene and a the subsequent development of aridity. To this end, we estimate divergence times and likely biogeographical origins of the major clades in the phylogeny of Heliotropium, using both Bayesian and likelihood methods. Divergence times of all Andean clades in Heliotropium are estimated to be of late Miocene or Pliocene ages. At least three independent Andean diversification events can be recognized within Heliotropium. Timing of the diversification in the Andean lineages Heliotropium sects.Heliothamnus, Cochranea, Heliotrophytum, Hypsogenia, Plagiomeris, Platygyne clearly correspond to a rapid, late Miocene uplift of the Andes and a Pliocene development of arid environments in South America.