Impaired fetal T cell development and perinatal lethality in mice lacking the cAMP response element binding protein

CREB, the cAMP response element binding protein, is a key transcriptional regulator of a large number of genes containing a CRE consensus sequence in their upstream regulatory regions. Mice with a hypomorphic allele of CREB that leads to a loss of the CREBα and Δ isoforms and to an overexpression of the CREBβ isoform are viable. Herein we report the generation of CREB null mice, which have all functional isoforms (CREBα, β, and Δ) inactivated. In contrast to the CREBαΔ mice, CREB null mice are smaller than their littermates and die immediately after birth from respiratory distress. In brain, a strong reduction in the corpus callosum and the anterior commissures is observed. Furthermore, CREB null mice have an impaired fetal T cell development of the αβ lineage, which is not affected in CREBαΔ mice on embryonic day 18.5. Overall thymic cellularity in CREB null mice is severely reduced affecting all developmental stages of the αβ T cell lineage. In contrast γδ T cell differentiation is normal in CREB mutant mice.

The Ran/TC4 GTPase-binding domain: identification by expression cloning and characterization of a conserved sequence motif.

Ran/TC4 is an essential, nuclear GTPase implicated in the initiation of DNA replication, entry into and exit from mitosis, and in nuclear RNA and protein transport through the nuclear pore complex. This diversity of functions suggests that Ran interacts with a large number of down-stream targets. Using an overlay assay, we detected a family of putative target proteins that associate with GTP-bound Ran. The sequence of only one such protein, HTF9a/RanBP1, is known. We have now cloned two additional Ran-binding proteins, allowing identification of a distinctive, highly conserved sequence motif of approximately 150 residues. This motif represents a minimal Ran-binding domain that stabilizes the GTP-bound state of Ran. The isolated domain also functions as a coactivator of Ran-GTPase-activating protein. Mutation of a conserved residue within the Ran-binding domain of HTF9a protein drastically reduced Ran binding. Ran-binding proteins coimmunoprecipitated with epitope-tagged Ran from cell lysates, suggesting that these proteins may associate in vivo. A previously uncharacterized Caenorhabditis elegans gene could encode a protein (96 kDa) possessing two Ran-binding domains. This open reading frame also contains similarities to nucleoporins, suggesting a functional link between Ran and nuclear pore complexes.

SnRK1-triggered switch of bZIP63 dimerization mediates the low-energy response in plants

Metabolic adjustment to changing environmental conditions, particularly balancing of growth and defense responses, is crucial for all organisms to survive. The evolutionary conserved AMPK/Snf1/SnRK1 kinases are well-known metabolic master regulators in the low-energy response in animals, yeast and plants. They act at two different levels: by modulating the activity of key metabolic enzymes, and by massive transcriptional reprogramming. While the first part is well established, the latter function is only partially understood in animals and not at all in plants. Here we identified the Arabidopsis transcription factor bZIP63 as key regulator of the starvation response and direct target of the SnRK1 kinase. Phosphorylation of bZIP63 by SnRK1 changed its dimerization preference, thereby affecting target gene expression and ultimately primary metabolism. A bzip63 knock-out mutant exhibited starvation-related phenotypes, which could be functionally complemented by wild type bZIP63, but not by a version harboring point mutations in the identified SnRK1 target sites.

Radium in Arctic surface water

The transpolar drift is strongly enriched in 228Ra accumulated on the wide Arctic shelves with subsequent rapid offshore transport. We present new data of Polarstern expeditions to the central Arctic and to the Kara and Laptev seas. Because 226Ra activities in Pacific waters are 30% higher than in Atlantic waters, we correct 226Ra for the Pacific admixture when normalizing 228Ra with 226Ra. The use of 228Ra decay as age marker critically depends on the constancy in space and time of the source activity, a condition that has not yet adequately been tested. While 228Ra decays during transit over the central basin, ingrowth of 228Th could provide an alternative age marker. The high 228Th/228Ra activity ratio (AR = 0.8-1.0) in the central basins is incompatible with a mixing model based on horizontal eddy diffusion. An advective model predicts that 228Th grows to an equilibrium AR, the value of which depends on the scavenging regime. The low AR over the Lomonosov Ridge (AR = 0.5) can be due to either rapid transport (minimum age without scavenging 1.1 year) or enhanced scavenging. Suspended particulate matter load (derived from beam transmission and particulate 234Th) and total 234Th depletion data show that scavenging, although extremely low in the central Arctic, is enhanced over the Lomonosov Ridge, making an age of 3 years more likely. The combined data of 228Ra decay and 228Th ingrowth confirm the existence of a recirculating gyre in the surface water of the eastern Eurasian Basin with a river water residence time of at least 3 years.