Myosin I is located at the leading edges of locomoting Dictyostelium amoebae

Movement of a eukaryotic cell along a substrate occurs by extension of lamellipodia and pseudopodia at the anterior and retraction at the posterior of the cell. The molecular and structural mechanisms of these movements are uncertain. Dictyostelium discoideum contains two forms of myosin. Here we show by immunofluorescence microscopy that non-filamentous myosin I occurs at the leading edges of the lamellipodial projections of migrating Dictyostelium amoebae, which are devoid of myosin II, whereas filamentous myosin II is concentrated in the posterior of the cells. On the basis of these locations of the two forms of myosin and their known biochemical and biophysical properties, we suggest that actomyosin I may contribute to the forces that cause extension at the leading edge of a motile cell, while the contraction of actomyosin II at the rear squeezes the cell mass forward. Myosin I isozymes might have similar roles in metazoan cells, for example at the leading edges of neuronal growth cones, and in the extension of lamellipodia and pseudopodia of leukocytes, macrophages and fibroblasts.     

Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome

ARC syndrome (OMIM 208085) is an autosomal recessive multisystem disorder characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with bile duct hypoplasia and low gamma glutamyl transpeptidase (gGT) activity. Platelet dysfunction is common. Affected infants do not thrive and usually die in the first year of life. To elucidate the molecular basis of ARC, we mapped the disease to a 7-cM interval on 15q26.1 and then identified germline mutations in the gene VPS33B in 14 kindreds with ARC. VPS33B encodes a homolog of the class C yeast vacuolar protein sorting gene, Vps33, that contains a Sec1-like domain important in the regulation of vesicle-to-target SNARE complex formation and subsequent membrane fusion.     

An outline of desensitization in pentameric ligand-gated ion channel receptors

Pentameric ligand-gated ion channel (pLGIC) receptors exhibit desensitization, the progressive reduction in ionic flux in the prolonged presence of agonist. Despite its pathophysiological importance and the fact that it was first described over half a century ago, surprisingly little is known about the structural basis of desensitization in this receptor family. Here, we explain how desensitization is defined using functional criteria. We then review recent progress into reconciling the structural and functional basis of this phenomenon. The extracellular–transmembrane domain interface is a key locus. Activation is well known to involve conformational changes at this interface, and several lines of evidence suggest that desensitization involves a distinct conformational change here that is incompatible with activation. However, major questions remain unresolved, including the structural basis of the desensitization-induced agonist affinity increase and the mechanism of pore closure during desensitization.     

Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer

Aberrant promoter methylation and the associated loss of gene expression is a common accompaniment of human cancers. Nonetheless, it has been challenging to demonstrate in any given tumour that methylation of a specific gene was causal and not consequent to malignant transformation. In this regard, our attention was drawn to the genesis of gastric cancers in individuals with hereditary diffuse gastric cancer (HDGC). These individuals harbour germline mutations in the gene encoding E-cadherin, CDH1, but their cancers have consistently demonstrated absence of loss of heterozygosity at the CDH1 locus. These findings suggested the hypothesis that CDH1 promoter methylation might function as the 'second genetic hit' in the genesis of these cancers.     

Karyotypic data for five species of anguid lizards

Zusammenfassung Die Chromosomensätze von 5 Eidechsenarten der Familie Aguidae, davon vier vom GenusGerrhonotus und eine vom GenusDiploglossus werden beschrieben.D. costatus ist 2n=36 mit 12 grossen metazentrischen Chromosomen und 24 Mikrochromosomen.G. multicarinatus ist 2n=48,G. paucicarinatus 2n=46 undG. coeruleus 2n=38. Diese 3 Arten haben einen identischen «nombre fondamentale» von 48 und alle haben 26 Mikrochromosomen.G. monticolus besitzt 2n=30. Die Anzahl der Mikrochromosomen ist auf 12 reduziert.     

Fate and characteristics of Picea damaged by Elatobium abietinum (Walker) (Homoptera: Aphididae) in the White Mountains of Arizona

Spruce aphid, Elatobium abietinum (Walker), is a new invasive pest in high-elevation forests of southwestern USA. Plots in the White Mountains of Arizona were evaluated over several years to assess the extent and severity of damage in high-elevation forests and to identify tree and site characteristics associated with defoliation and mortality. Large areas were defoliated in each of 4 recent outbreaks. Impact from a single defoliation episode included an overall mortality of 10.3% to Picea engelmannii Parry, 24%-41% in severely defoliated trees. Defoliation severity was much greater on P. engelmannii than on P. pungens Engelm. and was more severe in the lower canopy layers. Retention of foliage in the upper-crown third of individual trees was a critical factor in tree survivorship. Mortality was associated with defoliation severity and severe infection by Arceuthobium microcarpum (Engelmann) Hawksworth & Wiens. Picea pungens was much more susceptible to A. microcarpum more than was P. engelmannii . The combined effects of high levels of defoliation and mistletoe infection were lethal, resulting in almost 70% mortality. Mortality continued to occur at 3 years after defoliation. This aphid will affect natural disturbance regimes and tree population dynamics in mixed-conifer and spruce-fir forests of the American Southwest.