Megf10 regulates the progression of the satellite cell myogenic program

We identify here the multiple epidermal growth factor repeat transmembrane protein Megf10 as a quiescent satellite cell marker that is also expressed in skeletal myoblasts but not in differentiated myofibers. Retroviral expression of Megf10 in myoblasts results in enhanced proliferation and inhibited differentiation. Infected myoblasts that fail to differentiate undergo cell cycle arrest and can reenter the cell cycle upon serum restimulation. Moreover, experimental modulations of Megf10 alter the expression levels of Pax7 and the myogenic regulatory factors. In contrast, Megf10 silencing in activated satellite cells on individual fibers or in cultured myoblasts results in a dramatic reduction in the cell number, caused by myogenin activation and precocious differentiation as well as a depletion of the self-renewing Pax7⁺/MyoD⁻ population. Additionally, Megf10 silencing in MyoD^−/− myoblasts results in down-regulation of Notch signaling components. We conclude that Megf10 represents a novel transmembrane protein that impinges on Notch signaling to regulate the satellite cell population balance between proliferation and differentiation.     

ZAP-70 kinase regulates HIV cell-to-cell spread and virological synapse formation

HIV efficiently spreads in lymphocytes, likely through virological synapses (VSs). These cell-cell junctions share some characteristics with immunological synapses, but cellular proteins required for their constitution remain poorly characterized. We have examined here the role of ZAP-70, a key kinase regulating T-cell activation and immunological synapse formation, in HIV replication. In lymphocytes deficient for ZAP-70, or expressing a kinase-dead mutant of the protein, HIV replication was strikingly delayed. We have characterized further this replication defect. ZAP-70 was dispensable for the early steps of viral cycle, from entry to expression of viral proteins. However, in the absence of ZAP-70, intracellular Gag localization was impaired. ZAP-70 was required in infected donor cells for efficient cell-to-cell HIV transmission to recipients and for formation of VSs. These results bring novel insights into the links that exist between T-cell activation and HIV spread, and suggest that HIV usurps components of the immunological synapse machinery to ensure its own spread through cell-to-cell contacts.     

Expression of Hoxa2 in cells entering chondrogenesis impairs overall cartilage development

Vertebrate Hox genes act as developmental architects by patterning embryonic structures like axial skeletal elements, limbs, brainstem territories, or neural crest derivatives. While active during the patterning steps of development, these genes turn out to be down-regulated in specific differentiation programs like that leading to chondrogenesis. To investigate why chondrocyte differentiation is correlated to the silencing of a Hox gene, we generated transgenic mice allowing Cre-mediated conditional misexpression of Hoxa2 and induced this gene in Collagen 2 alpha 1-expressing cells committed to enter chondrogenesis. Persistent Hoxa2 expression in chondrogenic cells resulted in overall chondrodysplasia with delayed cartilage hypertrophy, mineralization, and ossification but without proliferation defects. The absence of skeletal patterning anomaly and the regular migration of precursor cells indicated that the condensation step of chondrogenesis was normal. In contrast, closer examination at the differentiation step showed severely impaired chondrocyte differentiation. In addition, this inhibition affected structures independently of their embryonic origin. In conclusion, for the first time here, by a cell-type specific misexpression, we precisely uncoupled the patterning function of Hoxa2 from its involvement in regulating differentiation programs per se and demonstrate that Hoxa2 displays an anti-chondrogenic activity that is distinct from its patterning function.     

Metal Ion availability in mitochondria

Transition metal ions are required for many aspects of mitochondrial physiology. Copper, iron, manganese and zinc are cofactors in metalloenzymes and metalloproteins within the organelle. Little is known how cells maintain optimal pools of these metal ions for mitochondrial function. This review documents the available literature on mitochondrial metal ion pools and protein metallation reactions. Upon perturbation in metal pools, mis-metallation reactions do occur. Thus, regulation of metal ion accessibility and bioavailability must exist.     

The Arabidopsis ATNRT2.7 nitrate transporter controls nitrate content in seeds

In higher plants, nitrate is taken up by root cells where Arabidopsis thaliana NITRATE TRANSPORTER2.1 (ATNRT2.1) chiefly acts as the high-affinity nitrate uptake system. Nitrate taken up by the roots can then be translocated from the root to the leaves and the seeds. In this work, the function of the ATNRT2.7 gene, one of the seven members of the NRT2 family in Arabidopsis, was investigated. High expression of the gene was detected in reproductive organs and peaked in dry seeds. beta-Glucuronidase or green fluorescent protein reporter gene expression driven by the ATNRT2.7 promoter confirmed this organ specificity. We assessed the capacity of ATNRT2.7 to transport nitrate in Xenopus laevis oocytes or when it is expressed ectopically in mutant plants deficient in nitrate transport. We measured the impact of an ATNRT2.7 mutation and found no difference from the wild type during vegetative development. By contrast, seed nitrate content was affected by overexpression of ATNRT2.7 or a mutation in the gene. Finally, we showed that this nitrate transporter protein was localized to the vacuolar membrane. Our results demonstrate that ATNRT2.7 plays a specific role in nitrate accumulation in the seed.     

Cotranslational protein folding--fact or fiction?

MOTIVATION: Experimentalists have amassed extensive evidence over the past four decades that proteins appear to fold during production by the ribosome. Protein structure prediction methods, however, do not incorporate this property of folding. A thorough study to find the fingerprint of such sequential folding is the first step towards using it in folding algorithms, so assisting structure prediction. RESULTS: We explore computationally the existence of evidence for cotranslational folding, based on large sets of experimentally determined structures in the PDB. Our perspective is that cotranslational folding is the norm, but that the effect is masked in most classes. We show that it is most evident in alpha/beta proteins, confirming recent findings. We also find mild evidence that older proteins may fold cotranslationally. A tool is provided for determining, within a protein, where cotranslation is most evident.     

Satellite and stem cells in muscle growth and repair

The FASEB summer research conference on Skeletal Muscle Satellite and Stem Cells, organized by Thomas Rando, Giulio Cossu and Jeffrey Chamberlain, was held in Indian Wells, California, in July. An international array of researchers gathered to share numerous new insights into the cellular and molecular regulation of stem cells and satellite cells in skeletal muscle biology. The conference is unique in that it brings together investigators from diverse backgrounds, who work on the growth and repair of skeletal muscle in humans and model systems, in health and disease.     

Effects of nutrients and warming on Planktothrix dynamics and diversity: a palaeolimnological view based on sedimentary DNA and RNA

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Role of Caribbean Islands in the diversification and biogeography of Neotropical Heraclides swallowtails

Numerous hypotheses on the evolution of Neotropical biodiversity have stimulated research to provide a better understanding of diversity dynamics and distribution patterns of the region. However, few studies integrate molecular and morphological data with complete sampling of a Neotropical group, and so there has been little synthesis of the multiple processes governing biodiversity through space and time. Here, a total‐evidence phylogenetic approach is used to reconstruct the evolutionary history of the butterfly subgenus Heraclides. We used DNA sequences for two mitochondrial genes and one nuclear gene and coded 133 morphological characters of larvae and adults. A robust and well‐resolved phylogeny was obtained using several analytical approaches, while molecular dating and biogeographical analyses indicated an early Miocene origin (22 Mya) in the Caribbean Islands. We inferred six independent dispersal events from the Caribbean to the mainland, and three from the mainland to the Caribbean, and we suggest that cooling climates with decreasing sea levels may have contributed to these events. The time‐calibrated tree is best explained by a museum model of diversity in which both speciation and extinction rates remained constant through time. By assessing both continental and fine‐scale biodiversity patterns, this study provides new findings, for instance that islands may act as source of diversity rather than as a sink, to explain spatio‐temporal macroevolutionary processes within the Neotropical region.