Neurotrophins: more to NGF than just survival

NGF's role in neuronal survival has tended to mask other potential functions. But now the generation of mice lacking both Bax - required for the death of NGF-deprived neurons - and NGF or its receptor has shown that NGF plays a key role in establishing cutaneous innervation and regulating neuropeptide expression.     

Preventing phagocytosis takes more than a sweet disposition

While a polysaccharide capsule is known to be important for preventing phagocytosis of the human pathogen Cryptococcus neoformans, other antiphagocytic pathways have been generally elusive. Now, a capsule-independent pathway has been identified that prevents macrophages from ingesting the fungus, contributing to evasion of the host immune response.     

Pattern formation: a new twist to BMP signalling

Dorsal-ventral patterning in Xenopus and Drosophila embryos involves BMP family signalling molecules. Twisted Gastrulation has now been added to the list of proteins that regulate the activity of these molecules, providing new insights into how BMPs are made available to their signalling receptors.     

Developmental biology: physics adds a twist to gut looping

Much of the effort in understanding the dynamic process of development has focused on dissecting biochemical pathways. Recent studies illustrate that simple physical forces are also important in patterning organs.     

Oncogenic Ras-induced expression of Noxa and Beclin-1 promotes autophagic cell death and limits clonogenic survival

Deregulated oncogenes such as MYC and RAS are typically insufficient to transform cells on their own due to the activation of pathways that restrain proliferation. Previous studies have shown that oncogenic H-Ras can induce proliferative arrest or senescence, depending on the cellular context. Here, we show that deregulated H-Ras activity can also lead to caspase-independent cell death with features of autophagy. Ras-induced autophagy was associated with upregulation of the BH3-only protein Noxa as well as the autophagy regulator Beclin-1. Silencing of Noxa or Beclin-1 expression reduced Ras-induced autophagy and increased clonogenic survival. Ras-induced cell death was also inhibited by coexpression of Bcl-2 family members that inhibit Beclin-1 function. Ras-induced autophagy was associated with Noxa-mediated displacement of the Bcl-2 family member, Mcl-1, from Beclin-1. Thus, Ras-induced expression of Noxa and Beclin-1 promotes autophagic cell death, which represents a mechanism to limit the oncogenic potential of deregulated Ras signals.     

Replicative helicases: a staircase with a twist

The first crystal structure of a ring helicase encircling single-stranded DNA reveals a mechanism for ATP-dependent DNA translocation.     

Potassium channels: watching a voltage-sensor tilt and twist

The fourth transmembrane helix (S4) is the primary voltage-sensor of voltage-gated ion channels. Recent studies have used fluorescence resonance energy transfer as a spectroscopic ruler to determine the nature and magnitude of the voltage-induced movement of S4 that leads to channel opening.     

SUMO-specific proteases: a twist in the tail

The small ubiquitin-like modifier (SUMO) is involved in many cellular processes and is required for normal growth and development in all eukaryotes. Whereas lower eukaryotes have a single version of SUMO, higher eukaryotes have three versions: SUMO-1, -2 and -3. Similarly to most other ubiquitin-like proteins, the primary translation products of the SUMO genes need to be proteolytically processed to expose the C-terminal glycine that will be linked to lysine side chains in substrates. Processing of SUMO precursors is mediated by SUMO-specific proteases that also remove SUMO from modified proteins and depolymerise poly-SUMO chains.     

Vomeronasal organ: pheromone recognition with a twist

Pheromones are detected by the vomeronasal organ using members of two receptor superfamilies: the V1Rs and V2Rs. New studies show that MHC class I molecules are co-expressed in particular combinations with specific V2Rs in the vomeronasal organ. The role of these MHC molecules is unknown, but they may be of considerable biological significance.     

Microtubule cytoskeleton: a new twist at the end

A diverse group of proteins known as +TIPs specifically recognize the growing plus ends of microtubules in cells. Two recent papers on one such protein, CLIP-170, provide new insights into the cellular functions of +TIPs as well as the mechanism by which they track microtubule ends.     

Tumor metastasis: a new twist on epithelial-mesenchymal transitions

Epithelial-mesenchymal transitions are essential for normal embryonic development and for progression of non-invasive tumor cells into malignant, metastatic carcinomas. Twist, an important regulator of morphogenesis in the embryo, has recently been implicated in the onset of invasive behavior during tumor progression.     

Torsional restraint: a new twist on frameshifting pseudoknots

mRNA pseudoknots have a stimulatory function in programmed −1 ribosomal frameshifting (−1 PRF). Though we previously presented a model for how mRNA pseudoknots might activate the mechanism for −1 PRF, it did not address the question of the role that they may play in positioning the mRNA relative to the ribosome in this process [E. P. Plant, K. L. M. Jacobs, J. W. Harger, A. Meskauskas, J. L. Jacobs, J. L. Baxter, A. N. Petrov and J. D. Dinman (2003) RNA, 9, 168–174]. A separate ‘torsional restraint’ model suggests that mRNA pseudoknots act to increase the fraction of ribosomes directed to pause with the upstream heptameric slippery site positioned at the ribosome's A- and P-decoding sites [J. D. Dinman (1995) Yeast, 11, 1115–1127]. Here, experiments using a series of ‘pseudo-pseudoknots’ having different degrees of rotational freedom were used to test this model. The results of this study support the mechanistic hypothesis that −1 ribosomal frameshifting is enhanced by torsional resistance of the mRNA pseudoknot.     

Silk from crickets: a new twist on spinning

Raspy crickets (Orthoptera: Gryllacrididae) are unique among the orthopterans in producing silk, which is used to build shelters. This work studied the material composition and the fabrication of cricket silk for the first time. We examined silk-webs produced in captivity, which comprised cylindrical fibers and flat films. Spectra obtained from micro-Raman experiments indicated that the silk is composed of protein, primarily in a beta-sheet conformation, and that fibers and films are almost identical in terms of amino acid composition and secondary structure. The primary sequences of four silk proteins were identified through a mass spectrometry/cDNA library approach. The most abundant silk protein was large in size (300 and 220 kDa variants), rich in alanine, glycine and serine, and contained repetitive sequence motifs; these are features which are shared with several known beta-sheet forming silk proteins. Convergent evolution at the molecular level contrasts with development by crickets of a novel mechanism for silk fabrication. After secretion of cricket silk proteins by the labial glands they are fabricated into mature silk by the labium-hypopharynx, which is modified to allow the controlled formation of either fibers or films. Protein folding into beta-sheet structure during silk fabrication is not driven by shear forces, as is reported for other silks.