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In Drosophila, primary spermatocytes of Hsp90 mutant males exhibit crystalline aggregates (8,9) (see also Fig. 1b), usually absent in wild-type testes (Fig. 1a), the formation of which is due to [...], The canalization concept (1) describes the resistance of a developmental process to phenotypic variation, regardless of genetic and environmental perturbations, owing to the existence of buffering mechanisms. Severe perturbations, which overcome such buffering mechanisms, produce altered phenotypes that can be heritable and can themselves be canalized by a genetic assimilation process. An important implication of this concept is that the buffering mechanism could be genetically controlled. Recent studies on Hsp90, a protein involved in several cellular processes and development pathways (2-5), indicate that it is a possible molecular mechanism for canalization and genetic assimilation. In both flies and plants, mutations in the Hsp90-encoding gene induce a wide range of phenotypic abnormalities, which have been interpreted as an increased sensitivity of different developmental pathways to hidden genetic variability (6,7). Thus, Hsp90 chaperone machinery may be an evolutionarily conserved buffering mechanism of phenotypic variance, which provides the genetic material for natural selection. Here we offer an additional, perhaps alternative, explanation for proposals of a concrete mechanism underlying canalization. We show that, in Drosophila, functional alterations of Hsp90 affect the Piwi-interacting RNA (piRNA; a class of germ-line-specific small RNAs) silencing mechanism leading to transposon activation and the induction of morphological mutants. This indicates that Hsp90 mutations can generate new variation by transposon-mediated 'canonical' mutagenesis.

Aldosterone has non-genomic effects that express within minutes and modulate intracellular ion milieu and cellular function. However, it is still undefined whether aldosterone actually alters intracellular ion concentrations or cellular [...]

We previously demonstrated that lactoferrin inhibits adherence of enteropathogenic Escherichia coli to HEp-2 cells and decreases invasiveness of Shigella flexneri in HeLa cells by disruption of the type III secretory [...]

In eukaryotes, the organization of chromatin into higher-order structures governs diverse chromosomal processes. Besides creating distinct metastable transcriptional domains during cellular differentiation, the formation of higher-order chromatin domains is widely [...], The higher-order assembly of chromatin imposes structural organization on the genetic information of eukaryotes and is thought to be largely determined by posttranslational modification of histone tails. Here, we study a 20-kilobase silent domain at the mating-type region of fission yeast as a model for heterochromatin formation. We find that, although histone H3 methylated at lysine 9 (H3 [Lys.sup.9]) directly recruits heterochromatin protein Swi6/HP1, the critical determinant for H3 [Lys.sup.9] rnethylation to spread in cis and to be inherited through mitosis and meiosis is Swi6 itself. We demonstrate that a centromerehomologous repeat (cenH) present at the silent mating-type region is sufficient for heterochromatin formation at an ectopic site, and that its repressive capacity is mediated by components of the RNA interference (RNAi) machinery. Moreover, cenH and the RNAi machinery cooperate to nucleate heterochromatin assembly at the endogenous mat locus but are dispensable for its subsequent inheritance. This work defines sequential requirements for the initiation and propagation of regional heterochromatic domains.

The discovery of intramembrane proteolysis has revealed alternative pathways in cell signaling, cell regulation, and protein processing (1). Dormant, membrane-bound transcription factors, like sterol regulatory element--binding protein (1), activating transcription [...], Signal peptide peptidase (SPP) catalyzes intramembrane proteolysis of some signal peptides after they have been cleaved from a preprotein. In humans, SPP activity is required to generate signal sequence--derived human lymphocyte antigen--E epitopes that are recognized by the immune system, and to process hepatitis C virus core protein. We have identified human SPP as a polytopic membrane protein with sequence motifs characteristic of the presenilin-type aspartic proteases. SPP and potential eukaryotic homologs may represent another family of aspartic proteases that promote intramembrane proteolysis to release biologically important peptides.

A domain is a region distinctively marked by some physical feature that distinguishes it from the surrounding landscape. A domain in a cellular membrane, therefore, is a region with physical [...], The surface membrane of cells is studded with morphologically distinct regions, or domains, like microvilli, cell-cell junctions, and coated pits. Each of these domains is specialized for a particular function, such as nutrient absorption, cell-cell communication, and endocytosis. Lipid domains, which include caveolae and rafts, are one of the least understood membrane domains. These domains are high in cholesterol and sphingolipids, have a light buoyant density, and function in both endocytosis and cell signaling. A major mystery, however, is how resident molecules are targeted to lipid domains. Here, we propose that the molecular address for proteins targeted to lipid domains is a lipid shell.

Cadherins are thought to be the primary mediators of adhesion between the cells of vertebrate animals, and they also function in cell adhesion in many invertebrates (1-4). The expression of [...], Cadherins are transmembrane proteins that mediate adhesion between cells in the so[id tissues of animals. Here we present the 3.1 angstrom resolution crystal structure of the whole, functional extracellular domain from C-cadherin, a representative 'classical' cadherin. The structure suggests a molecular mechanism for adhesion between cells by classical cadherins, and it provides a new framework for understanding both cis (same cell) and trans (juxtaposed cell) cadherin interactions. The trans adhesive interface is a twofold symmetric interaction defined by a conserved tryptophan side chain at the membrane-distal end of a cadherin molecule from one cell which inserts into a hydrophobic pocket at the membrane-distal end of a cadherin molecule from the opposing cell.

Recent studies have opened up the biochemistry underlying the dynamics and structural organization of actin in lamellipodia. Arp2/3 complex plays a key role in actin polymerization, promoting nucleation and dendritic [...], Lamellipodia are thin, veil-like extensions at the edge of cells that contain a dynamic array of actin filaments. We describe an approach for analyzing spatial regulation of actin polymerization and depolymerization in vivo in which we tracked single molecules of actin fused to the green fluorescent protein. Polymerization and the lifetime of actin filaments in lamellipodia were measured with high spatial precision. Basal polymerization and depolymerization occurred throughout lamellipodia with largely constant kinetics, and polymerization was promoted within one micron of the lamellipodium tip. Most of the actin filaments in the lamellipodium were generated by polymerization away from the tip.

The ability of rodents to learn and remember features of a new environment is thought to require the formation in the animal's brain of a cognitive map--a neural representation of [...], Hippocampal pyramidal cells are called place cells because each cell tends to fire only when the animal is in a particular part of the environment-the cell's firing field. Acute pharmacological blockade of N-methyl-D-aspartate (NMDA) glutamate receptors was used to Investigate how NMDA-based synaptic plasticity participates in the formation and maintenance of the firing fields. The results suggest that the formation and short-term stability of firing fields in a new environment involve plasticity that is independent of NMDA receptor activation. By contrast, the long-term stabilization of newly established firing fields required normal NMDA receptor function and, therefore, may be related to other NMDA-dependent processes such as long-term potentiation and spatial learning.

Introduction The nervous system in tentacles associated with feeding in sea anemones includes ciliated sensory cells oriented perpendicularly to the surface and ganglion cells located above the basoepithelial musculature (Westfall, [...], Nerve cells from tentacles of the sea anemone Calliactis parasitica were dissociated in 1000 units/ml of collagenase for scanning electron microscopic studies and in 0.125% elastase followed by 12 units/ml of ficin for cell counts using light microscopy. The studies revealed 33 distinguishable neuronal shapes, which were categorized as either sensory cells having an apical cilium or ganglion cells with or without a perikaryal cilium and further subdivided into unipolar, bipolar and multipolar neurons based on the number of processes that extended from the perikaryon. Unipolar sensory cells were characterized by an apical cilium adjacent to the perikaryon and a long, simple or terminally branched axon. Unipolar ganglion cells lacked an apical cilium. Bipolar sensory cells had a neck between the cilium and perikaryon and an oppositely directed axon. Bipolar ganglion cells had isopolar processes or asymmetrical processes, which were simple or complexly branched. One type of bipolar ganglion cell with isopolar processes had a perikaryal cilium. Multipolar sensory cells had a distinct neck between the perikaryon and the cilium and two or more simple or complexly branched processes extending from the triangularly shaped cell body. Multipolar ganglion cells had variously shaped perikarya from which extended three or more short or long processes that were simple or complexly branched. One type of tripolar ganglion cell had a perikaryal cilium. The different types of nerve cells were quantified, and statistical comparisons were made.

Since the publication of the cell theory (Schleiden 1838, Schwann 1839), 'the cell is the building stone of the organism' (Heidenhain 1907) has become one of the great slogans in [...]