Actin in action: the interplay between the actin cytoskeleton and synaptic efficacy

Synapse regulation exploits the capacity of actin to function as a stable structural component or as a dynamic filament. Beyond its well-appreciated role in eliciting visible morphological changes at the synapse, the emerging picture points to an active contribution of actin to the modulation of the efficacy of pre- and postsynaptic terminals. Moreover, by engaging distinct pools of actin and divergent signalling pathways, actin-dependent morphological plasticity could be uncoupled from modulation of synaptic strength. The aim of this Review is to highlight some of the recent progress in elucidating the role of the actin cytoskeleton in synaptic function.     

Lycoparins A-C, new alkaloids from Lycopodium casuarinoides inhibiting acetylcholinesterase

Three new Lycopodium alkaloids, lycoparins A-C (1-3), have been isolated from the club moss Lycopodium casuarinoides. Structures and stereochemistry of 1-3 were elucidated on the basis of 2D NMR correlations. Lycoparins C (3) exhibited an inhibitory activity against acetylcholinesterase, while lycoparins A (1) and B (2) did not show activity.     

Characterization of the {alpha}-helix region in domain 3 of the haemolytic lectin CEL-III: implications for self-oligomerization and haemolytic processes

CEL-III is a haemolytic lectin, which has two beta-trefoil domains (domains 1 and 2) and a beta-sheet-rich domain (domain 3). In domain 3 (residues 284-432), there is a hydrophobic region containing two alpha-helices (H8 and H9, residues 317-357) and a loop between them, in which alternate hydrophobic residues, especially Val residues, are present. To elucidate the role of the alpha-helix region in the haemolytic process, peptides corresponding to different parts of this region were synthesized and characterized. The peptides containing the sequence that corresponded to the loop and second alpha-helix (H9) showed the strongest antibacterial activity for Staphylococcus aureus and Bacillus subtilis through a marked permeabilization of the bacterial cell membrane. The recombinant glutathione S-transferase (GST)-fusion proteins containing domain 3 or the alpha-helix region peptide formed self-oligomers, whereas mutations in the alternate Val residues in the alpha-helix region lead to decreased oligomerization ability of the fusion proteins. These results suggest that the alpha-helix region, particularly its alternate Val residues are important for oligomerization of CEL-III in target cell membranes, which is also required for a subsequent haemolytic action.     

Inference of the japonica rice domestication process from the distribution of six functional nucleotide polymorphisms of domestication-related genes in various landraces and modern cultivars

Crop domestication can serve as a model of plant evolutionary processes. It involves a series of selection events from standing natural variation and newly occurring mutations and combinations of mutations as a result of natural crossings in populations during local adaptation and propagation of plant lines to other cultivation areas. Our earlier identification of three functional nucleotide polymorphisms (FNPs) of distinct genes involved in the rice domestication process led us to propose a model of the japonica rice domestication process. Here, we examined three more FNPs in two domestication-related genes involved in pigment synthesis during the development of seed pericarp color (Rc and Rd) in 91 landraces (and some modern cultivars) of japonica rice collected from throughout the area of distribution of rice. These polymorphisms were assigned by using genome-wide patterns of restriction fragment length polymorphisms (RFLPs) and the local origins of the landraces. The results led us to infer the process of japonica rice domestication in more detail and propose a more refined model of the japonica domestication process. In this model, the critical role of the Rc FNP at an early step of the domestication process was highlighted. Independent artificial selections of two defective Rd alleles were found, suggesting a role for Rd other than in pigment synthesis during rice domestication.     

Cardiovascular disease risk among atomic bomb survivors exposed in utero, 1978-2003

Tatsukawa, Y., Nakashima, E., Yamada, M., Funamoto, S., Hida, A., Akahoshi, M., Sakata, R., Ross, N. P., Kasagi, F., Fujiwara, S. and Shore, R. E. Cardiovascular Disease Risk among Atomic Bomb Survivors Exposed In Utero, 1978-2003. Radiat. Res. 170, 269-274 (2008).Given the well-documented association of in utero radiation exposure with childhood cancer and developmental impairments, the possibility of effects on adult onset diseases is an important issue. The objectives of the present study were to examine the effects of atomic bomb radiation dose on the incidence of hypertension, hypercholesterolemia and cardiovascular disease (myocardial infarction and stroke) among survivors exposed in utero and to compare their risk estimates with those of survivors exposed in childhood (<10 years old) at the time of the bombing. A total of 506 participants exposed in utero and 1,053 participants exposed in childhood were followed during 1978-2003 with biennial clinical examinations. There were no significant radiation dose effects for any diseases in the entire in utero-exposed cohort or in trimester-of-exposure subgroups, though there was a suggestion of an increased risk when fatal and nonfatal cardiovascular disease cases were combined. Positive radiation dose effects were found for hypertension and cardiovascular disease in the childhood-exposure cohort, but there were no statistically significant differences in the relative risks when we compared the two cohorts. Since the in utero cohort was under age 60 at the latest examination, continued follow-up is needed to document cardiovascular disease risk more fully.     

Arabidopsis Aux/IAA genes are involved in brassinosteroid-mediated growth responses in a manner dependent on organ type

We examined whether auxin/indole-3-acetic acid (Aux/IAA) proteins, which are key players in auxin-signal transduction, are involved in brassinosteroid (BR) responses. iaa7/axr2-1 and iaa17/axr3-3 mutants showed aberrant BR sensitivity and aberrant BR-induced gene expression in an organ-dependent manner. Two auxin inhibitors were tested in terms of BR responses. Yokonolide B inhibited BR responses, whereas p-chlorophenoxyisobutyric acid did not inhibit BR responses. DNA microarray analysis revealed that 108 genes were up-regulated, while only eight genes were down-regulated in iaa7. Among the genes that were up- or down-regulated in axr2, 22% were brassinolide-inducible genes, 20% were auxin-inducible genes, and the majority were sensitive neither to BR nor to auxin. An inhibitor of BR biosynthesis, brassinazole, inhibited auxin induction of the DR5-GUS gene, which consists of a synthetic auxin-response element, a minimum promoter, and a beta-glucuronidase. These results suggest that Aux/IAA proteins function in auxin- and BR-signaling pathways, and that IAA proteins function as the signaling components modulating BR sensitivity in a manner dependent on organ type.     

Diet-induced epigenetic regulation in vivo of the intestinal fructose transporter Glut5 during development of rat small intestine

Metabolic complications arising from excessive fructose consumption are increasing dramatically even in young children, but little is known about ontogenetic mechanisms regulating Glut5 [glucose transporter 5; encoded by the Slc2a5 (solute carrier family 2 member 5) gene]. Glut5 expression is low postnatally and does not increase, unless luminal fructose and systemic glucocorticoids are present, until ≥ 14 days of age, suggesting substrate-inducible age- and hormone-sensitive regulation. In the present study, we perfused intestines of 10- and 20-day-old rats with either fructose or glucose then analysed the binding of Pol II (RNA polymerase II) and GR (glucocorticoid receptor), as well as acetylation of histones H3 and H4 by chromatin immunoprecipitation. Abundance of Glut5 mRNA increased only with fructose perfusion and age, a pattern that matched that of Pol II binding and histone H3 acetylation to the Glut5 promoter. Although many regions of the Glut5 promoter respond to developmental signals, fewer regions perceive dietary signals. Age- but not fructose-dependent expression of Sglt1 [sodium-dependent glucose co-transporter 1 encoded by the Slc5a1(solute carrier family 5 member 1) gene] also correlated with Pol II binding and histone H3 acetylation. In contrast, G6Pase (glucose-6-phosphatase; encoded by the G6pc gene) expression, which decreases with age and increases with fructose, is associated only with age-dependent changes in histone H4 acetylation. Induction of Glut5 during ontogenetic development appears to be specifically mediated by GR translocation to the nucleus and subsequent binding to the Glut5 promoter, whereas the glucocorticoid-independent regulation of Sglt1 by age was not associated with any GR binding to the Sglt1 promoter.