Editors' Choice

Science  12 Nov 2004:
Vol. 306, Issue 5699, pp. 1103

    Endocytosis at the Hub

    1. Stella M. Hurtley

    In clathrin-mediated endocytosis, a network of proteins assembles on the cytoplasmic surface of the plasma membrane and promotes the pinching off of a membrane-bounded clathrin-coated vesicle. Together, the proteins select cargoes that are carried either inside the vesicle or in its membrane, modify the shape of the membrane, and drive invagination, vesicle scission, and eventual uncoating. A key player in this process is the AP2 clathrin adaptor protein, which is involved in concentrating selected cargo in the newly forming clathrin-coated pits.

    In protein interaction networks, hubs are proteins that have disproportionately high numbers of interaction partners; in biological processes, hubs provide a temporal or spatial ordering to protein interactions. Praefcke et al. treat clathrin-mediated endocytosis as a module of a network and show how the α-appendage part of the AP2 protein works as an interaction hub. Only after being concentrated at sites of endocytosis do the appendages provide a multivalent binding platform (hub) for interaction partners (i.e., endocytic cargoes or other cargo adaptors). Thus, the partners will then be represented according to their relative affinities and concentrations in endocytic clathrin-coated pits and vesicles, even though any individual interactions will have been transient. — SMH

    EMBO J. 10.1038/sj.emboj.7600445 (2004).


    Registering Nanostructures

    1. Ian S. Orborne

    The manipulation of atoms using scanning tunneling microscopy (STM) has long promised the ability to fabricate nanometer- and atomic-scale electronic device structures. However, the realization of robust devices has been a difficult goal to attain simply because of the engineering problem of making electrical contact to the fabricated structure. The problem is that once the sample is removed from the ultrahigh vacuum where the STM atomic manipulation has taken place, the actual location of the structure is lost, particularly those regions that are buried under several layers of epitaxially grown semiconductor material. Ruess et al. have used a registration technique that allows the alignment of macroscopic electrodes to the nanoscale device elements buried underneath. The registration markers are etched into the substrate before the STM manipulation stage and so should be a general method for bottom-up fabrication of other nanoscale device structures. — ISO

    Nano Lett. 4, 1969 (2004).


    Taking Inventory

    1. Brooks Hanson

    An enormous amount of methane, an important greenhouse gas, is stored in sediments in the ocean basins as icy methane clathrate and as gas trapped by this ice and by sediments. Catastrophic release of methane from this warehouse has been suggested to have caused abrupt climate change (warming) in the past, and there are concerns that a warmer future climate may destabilize this reservoir, which would enhance warming further.

    To assess the amount of clathrate stored and to evaluate its stability, Buffett and Archer developed a mechanistic model for clathrate dynamics based on experimental and theoretical data on its stability and on factors affecting its formation and release, such as the supply of carbon to sediments and its diagenesis, storage, and oxygen content. Application to the current ocean basin implies that the global inventory is on the order of 1018 g of carbon stored as methane gas and clathrate. The modeling results imply that increasing temperature would likely deplete this inventory considerably; rebuilding would take several million years. The model also reveals that unless the oxygen content of the deep oceans was lower than at present, not enough methane would have been stored to account for the carbon isotope shift and the abrupt warming at the Paleocene-Eocene boundary, about 55 million years ago. — BH

    Earth Planet. Sci. Lett. 227, 185 (2004).


    Three in One

    1. Stephen J. Simpson

    Vaccines are designed to generate robust immunity through the coactivation of the adaptive and innate arms of the immune system. This is achieved by steering tripartite responses to antigenic epitopes by helper T (TH) cells, antigen-presenting dendritic cells (DCs), and antibody-producing B cells or the cytotoxic lymphocytes (CTLs) that ultimately execute pathogen clearance. However, the poor inherent immunogenicity of peptide epitopes favored in some vaccine formulas dictates the need for including complex and potentially toxic adjuvants that stimulate the essential priming activity of DCs.

    Jackson et al. have refined this approach by synthesizing structures containing TH epitopes coupled to B cell or CTL target epitopes. These were linked via a lipid moiety, which served to activate DCs through binding and activation of the innate signaling receptor TLR2. With different epitope combinations, strong antibody and CTL responses could be elicited in models of viral and bacterial infection, as well as to tumors, and were comparable to responses to an adjuvant traditionally used in vaccines. The ability to combine adjuvant and antigenic properties in a single synthetic formula offers an attractive approach for future vaccine design. — SJS

    Proc. Natl. Acad. Sci. U.S.A. 101, 15440 (2004).


    Weight Control: It Takes a Village

    1. Paula Kiberstis

    About 250 million adults worldwide are obese, a condition that puts them at great risk for diabetes, heart disease, and other serious health problems. Although remarkable progress has been made in understanding the physiological and environmental factors that regulate body weight in mammals, much remains to be learned.

    A new study in mice points to a surprising participant in body weight control: the community of bacteria (microbiota) that colonize the gut. Bäckhed et al. found that when they introduced the gut microbiota of normal mice into a special strain of “germ-free” mice, the recipients showed a 60% increase in total body fat within 2 weeks, even though they had eaten less and exhibited an increased metabolic rate. The microbiota appeared to promote fat storage by stimulating the synthesis of triglycerides in the liver and their deposition in adipocytes (fat cells). Based on their results, the authors hypothesize that changes in microbial ecology prompted by Western diets or differences in microbial ecology between individuals living in Western societies may affect predisposition toward obesity. — PAK

    Proc. Natl. Acad. Sci. U.S.A. 101, 15718 (2004).


    Keeping One's Head

    1. Marc S. Lavine

    Foam consists of a mass of bubbles—air trapped within thin liquid shells—that forms on agitation, such as when beer is poured into a glass. The stability of a foam depends on the nature of the liquid: evanescent in some cases, hardier in others because of additives that extend their lifetime. Surfactants, occasionally in conjunction with solid particles, are used as stabilizers because they reduce the surface tension of the liquid, preventing the bubbles from coalescing.

    Alargova et al. have found that polymer microrods made from an epoxy-based photoresist can stabilize foams so that they resist collapse even when most of the liquid is allowed to evaporate. In contrast to foams made with the common household detergent sodium dodecyl sulfate, which survived for 2 days, the polymer rod foams were stable for more than 2 weeks. The authors speculate that the greater stability is due to two factors. First, the rods induce a much thicker liquid layer between the air bubbles, and these layers sterically repulse each other, thus preventing coalescence of the bubbles. Second, the rods within a layer form an intertwined network, thus increasing its overall strength and also imparting to the bubbles a spherical shape, which tends to be highly unstable in ordinary foams. — MSL

    Langmuir 10.1021/la048647a (2004).


    Treasure Trove

    1. Gilbert J. Chin

    Many bioactive small molecules were originally identified by screening extracts from microorganisms. These so-called natural products, some possessing medicinal value, then became the targets of structure determination and total synthesis. Traditional production methods depended on being able to pinpoint the source of the metabolite and to cultivate high-yielding strains of the isolated organism, but molecular biological advances have made it feasible to look directly for the genetic components of the biosynthetic pathways.

    Piel et al. have extracted from the marine sponge Theonella swinhoei the gene clusters encoding the enzymes that make the polyketide onnamide A. Analysis of the gene structure indicates that their true source is probably an as-yet-unidentified bacterial symbiont, possibly of the Pseudomonas genus, harbored by the sponge. — GJC

    Proc. Natl. Acad. Sci. U.S.A. 101, 16222 (2004).