Avoiding the SCAMs

Dendrites from the same neuron usually avoid contact with one another, a behavior known as self-avoidance. In this issue of Neuron and in the upcoming May 4, 2007 issue of Cell, a pair of studies by Soba et al. and Hughes et al. and a study by Matthews et al., respectively, identify products from the highly alternatively spliced Dscam gene as central to this behavior in Drosophila. Signaling induced by adhesion between identical isoforms triggers repulsion between sister dendrites.     

Descrambling Dscam diversity

Neuronal processes exhibit exquisitely complex branching patterns crucial for the formation of distinct neural circuits. In this issue of Cell, Chen et al. (2006) show that the isoform diversity of the Dscam protein in Drosophila is required to establish stereotypical axonal branching patterns, suggesting that nonrandom expression of Dscam alternative splice variants determines neural connectivity.     

H3K27 demethylases, at long last

Methylation of lysine 27 on histone H3 (H3K27me) by the Polycomb complex (PRC2) proteins is associated with gene silencing in many developmental processes. A cluster of recent papers (Agger et al., 2007; De Santa et al., 2007; Lan et al., 2007; Lee et al., 2007) identify the JmjC-domain proteins UTX and JMJD3 as H3K27-specific demethylases that remove this methyl mark, enabling the activation of genes involved in animal body patterning and the inflammatory response.     

A backup DNA repair pathway moves to the forefront

Chromosomal translocations between antigen receptor loci and oncogenes are a hallmark of lymphoid cancers. Several new studies now reveal that programmed DNA breaks created during assembly of antigen receptor genes can be channeled into an alternative DNA end-joining pathway that is implicated in the chromosomal translocations of lymphoid cancers (Corneo et al., 2007; Soulas-Sprauel et al., 2007; Yan et al., 2007).     

Mighty Piwis defend the germline against genome intruders

Piwis are a germline-specific subclass of the Argonaute family of RNA interference (RNAi) effector proteins that are associated with a recently discovered group of small RNAs (piRNAs). Recent studies in Drosophila and zebrafish directly implicate Piwi proteins in piRNA biogenesis to maintain transposon silencing in the germline genome (Brennecke et al., 2007; Gunawardane et al., 2007; Houwing et al., 2007). This function may be conserved in mice as loss of Miwi2, a mouse Piwi homolog, leads to germline stem cell and meiotic defects correlated with increased transposon activity (Carmell et al., 2007).     

After hours keeps clock researchers CRYing Overtime

Three recent reports, including one in this issue of Cell, reveal that the circadian regulator CRY is targeted for degradation by the F box E3 ubiquitin ligase FBXL3 (Siepka et al., 2007; Busino et al., 2007; Godinho et al., 2007). These studies confirm the importance of targeted protein degradation as a key design feature of the mammalian circadian clock.     

Bone remodeling, energy metabolism, and the molecular clock

The adult skeleton is constantly renewed through bone remodeling. Four recent papers (Baldock et al., 2007; Lee et al., 2007; Lundberg et al., 2007; Sato et al., 2007) provide new insights into central and peripheral control of this remodeling sequence. Two of the studies add to our knowledge of the complex hypothalamic modulation of bone turnover mediated by NMU and NPY via the sympathetic nervous system, while the other two focus on the peripheral neural target, the osteoblast, and its regulation by neuropeptides and osteocalcin. These findings support a new paradigm concerning the regulation of bone remodeling and provide a foundation for novel approaches to preventing osteoporosis.     

Epigenetic Variations in Plant Hybrids and Their Potential Roles in Heterosis

Heterosis,one of the most important biological phenomena,refers to the phenotypic superiority of a hybrid over its genetically diverse parents with respect to many traits such as biomass,growth rate and yield.Despite its successful application in breeding and agronomic production of many crop and animal varieties,the molecular basis of heterosis remains elusive.The classic genetic explanations for heterosis centered on three hypotheses:dominance (Davenport,1908;Bruce,1910;Keeble and Pellew,1910;Jones,1917),overdominance (East,1908;Shull,1908) and epistasis (Powers,1944;Yu et al.,1997).However,these hypotheses are largely conceptual and not connected to molecular principles,and are therefore insufficient to explain the molecular basis of heterosis (Birchler et al.,2003).Recently,many studies have explored the molecular mechanism of heterosis in plants at a genome-wide level.These studies suggest that global differential gene expression between hybrids and parental lines potentially contributes to heterosis in plants (e.g.,Swanson-Wagner et al.,2006;Zhang et al.,2008;Wei et al.,2009;Song et al.,2010).Research suggests that genetic components,including cis-acting elements and trans-acting factors,are critical regulators of differential gene expression in hybrids (Hochholdinger and Hoecker,2007;Springer and Stupar,2007;Zhang et al.,2008).However,other research indicates that epigenetic components,the regulators of chromatin states and genome activity,also have the potential to impact heterosis (e.g.,Ha et al.,2009;He et al.,2010;Groszmann et al.,2011;Barber et al.,2012;Chodavarapu et al.,2012;Greaves et al.,2012a;Shen et al.,2012).     

Smac mimetics and TNFalpha: a dangerous liaison?

Inhibitor of apoptosis proteins (IAPs) such as XIAP, cIAP1, and cIAP2 are upregulated in many cancer cells. It has been thought that small-molecule mimetics of Smac, an endogenous IAP antagonist, might potentiate apoptosis in cancer cells by promoting caspase activation. However, three recent papers, two in Cell (Vince et al., 2007; Varfolomeev et al., 2007) and one in Cancer Cell (Petersen et al., 2007), now report that Smac mimetics primarily kill cancer cells via a different mechanism, the induction of autoubiquitination and degradation of cIAPs, which culminates in TNFalpha-mediated cell death.     

BDNF instructs the kinase LKB1 to grow an axon

Determining which neurite of a differentiating neuron is to become the axon is a crucial step in neuronal morphogenesis. Two groups (Barnes et al., 2007; Shelly et al., 2007) now report that axon specification in vivo is mediated by extracellular signals acting through the serine/threonine kinase LKB1.     

Neuronal glucose sensing: still a physiological orphan?

Although hypothalamic glucose sensing is a long-established phenomenon, its physiological role remains unclear. New studies (Parton et al., 2007; Claret et al., 2007) disrupting glucose sensing in pro-opiomelanocortin neurons via differing methods have yielded disparate energy and glucose homeostasis phenotypes, suggesting that neuronal glucose sensing is not critical for these processes.     

Inositol pyrophosphate pyrotechnics

Physiologic roles of highly phosphorylated inositol phosphates, including those containing pyrophosphate groups, have been the focus of much recent interest. In the April 6, 2007 issue of Science, two papers (Lee et al., 2007; Mulugu et al., 2007) demonstrate the occurrence of a novel inositol pyrophosphate molecule in yeast and elucidate its role in phosphate homeostasis.     

A two-way street: LSD1 regulates chromatin boundary formation in S. pombe and Drosophila

Two recent studies in Molecular Cell (Lan et al., 2007; Rudolph et al., 2007) implicate histone demethylation by LSD1 in the regulation of boundaries between silenced and active chromatin domains in both fission yeast and flies, but by distinct mechanisms.     

miRNAs play a tune

Two new studies describe functionally relevant interactions between microRNAs (miRNAs) and their targets in the immune system and the brain (Xiao et al., 2007; Karres et al., 2007). Furthermore, these studies illustrate the involvement of miRNAs in tuning the expression of target genes to physiologically relevant levels.     

A new acid mix enhances phosphopeptide enrichment on titanium- and zirconium dioxide for mapping of phosphorylation sites on protein complexes

The selective enrichment of phosphorylated peptides prior to reversed-phase separation and mass spectrometric detection significantly improves the analytical results in terms of higher number of detected phosphorylation sites and spectra of higher quality. Metal oxide chromatography (MOC) has been recently described for selective phosphopeptide enrichment (Pinkse et al., 2004 [1]; Larsen et al., 2005 [2]; Kweon and Hakansson, 2006 [3]; Cantin et al., 2007 [4]; Collins et al., 2007 [5]). In the present work we have tested the effect of a modified loading solvent containing a novel acid mix and optimized wash conditions on the efficiency of TiO₂-based phosphopeptide enrichment in order to improve our previously published method (Mazanek et al., 2007 [6]). Applied to a test mixture of synthetic and BSA-derived peptides, the new method showed improved selectivity for phosphopeptides, whilst retaining a high recovery rate. Application of the new enrichment method to digested purified protein complexes resulted in the identification of a significantly higher number of phosphopeptides as compared to the previous method. Additionally, we have compared the performance of TiO₂ and ZrO₂ columns for the isolation and identification of phosphopeptides from purified protein complexes and found that for our test set, both media performed comparably well. In summary, our improved method is highly effective for the enrichment of phosphopeptides from purified protein complexes prior to mass spectrometry, and is suitable for large-scale phosphoproteomic projects that aim to elucidate phosphorylation-dependent cellular processes.     

The high road and the low road: trafficking choices in plants

Polar transport of the signaling molecule auxin is critical for plant development and depends on both the polar distribution of auxin efflux carriers, which pump auxin out of the cell and the alignment of these polarized cells. Two papers in this issue of Cell (Michniewicz et al., 2007; Jaillais et al., 2007) address how polar transport of these carriers occurs and describe the endosomal pathways involved.     

The centrosome opens the way to mitosis

During mitosis, the interaction between chromosomes and microtubules requires nuclear envelope disassembly in prophase. Two articles in this issue of Developmental Cell show that centrosomes have a role in promoting nuclear envelope breakdown (Hachet et al., 2007; Portier et al., 2007). Surprisingly, the role of the centrosome in this process is independent of its role as a microtubule nucleation organelle. Instead, the centrosome seems to act as a spatial regulator for the activation of the Aurora A kinase.