In This Issue
BIOPHYSICS
Myosin Va flexibility across cytoskeletal junctions
Intracellular organelle transport from the cell center to the periphery involves two types of movement: kinesin first binds a vesicle and then “walks” for long distances along microtubules before handing off its cargo to vertebrate myosin Va, which moves along actin tracks for local delivery. How these two molecular motors find each other within the complex cytoskeletal network is still unknown. Yusuf Ali et al. investigated the ability of myosin Va ability to maneuver its way through both actin filament intersections and along actin–microtubule junctions. Myosin Va proved to be flexible, stepping past actin filament intersections. When myosin Va encountered a microtubule, the motor appeared to step onto the microtubule, where it began a one-dimensional diffusive search. Electrostatic interactions governed this association. Ali et al. say that this molecular movement may allow myosin Va to scan for kinesin and bind its cargo. — F.A.
Myosin Va at microtubule intersection.
“Myosin Va maneuvers through actin intersections and diffuses along microtubules” by M. Yusuf Ali, Elena B. Krementsova, Guy G. Kennedy, Rachel Mahaffy, Thomas D. Pollard, Kathleen M. Trybus, and David M. Warshaw (see pages 4332–4336)
BIOPHYSICS
Protein sequence predicts protein–protein networks
From transcriptional regulation to enzymatic cascades, protein–protein interactions (PPIs) govern nearly all biological processes. Juwen Shen et al. developed a method for predicting protein interactions based solely on protein sequence information. The authors' method relies on a machine learning algorithm, called support vector machine, combined with a conjoint triad feature and a kernel function. The conjoint triad method reduced the complexity of the vectors by regarding any three continuous amino acids as a single unit, with the kernel function factored in the symmetrical nature of the interactions. Using this algorithm, a vector space consisting of amino acids, clustered into several classes according to polarity and size, represents each protein sequence. The authors used >16,000 diverse PPI pairs to construct the universal model of protein interactions. The prediction ability of the approach reached >80% accuracy and detected several types of PPI networks, including complex crossover networks, in which multicore protein networks and one-core networks interact. Shen et al. say that their method may help in the design of therapeutics that interrupt disease-related protein networks rather than inhibiting individual target proteins. — F.A.
PPI network for CD9.
“Predicting protein—protein interactions based only on sequences information” by Juwen Shen, Jian Zhang, Xiaomin Luo, Weiliang Zhu, Kunqian Yu, Kaixian Chen, Yixue Li, and Hualiang Jiang (see pages 4337–4341)
ENVIRONMENTAL SCIENCES
Tropical fish extinctions alter nutrient recycling
Fish are integral components of aquatic food webs, particularly in tropical areas where fish diversity is high. Human influences such as overfishing and habitat alteration threaten to reduce species richness in these areas, which may result in profound ecosystem effects. Peter McIntyre et al. assessed how one key role of fish, nutrient recycling, might be affected by species extinctions. The authors first estimated nitrogen and phosphorus excretion by each fish species in the diverse faunas of two tropical sites, Rio Las Marias in Venezuela and Africa's Lake Tanganyika. These measurements were followed by probabilistic simulations of how extinctions would alter nitrogen and phosphorus recycling rates and ratios. McIntyre et al. found that random extinctions led to a linear decline of nitrogen and phosphorus recycling in both ecosystems, although compensatory responses by surviving species could minimize the decline until over half the fish species were eliminated. Nonrandom extinctions produced divergent results, and the sharpest declines occurred when extinctions were based on fishing pressure rather than body size or trophic position. The authors note that major fishery species often combine large body size and high population density, and these same characteristics give them an important role in nutrient recycling. — N.Z.
Limnotilapia dardennii, an important species in fisheries of Lake Tanganyika near Kigoma, Tanzania.
“Fish extinctions alter nutrient recycling in tropical freshwaters” by Peter B. McIntyre, Laura E. Jones, Alexander S. Flecker, and Michael J. Vanni (see pages 4461–4466)
IMMUNOLOGY
Clonal expansion self-limited by competition
In clonal expansion, a key stage in the immune response, a few T cells rapidly expand to a population of millions. Stable conjugation with antigen-presenting dendritic cells (DCs) is essential for full T cell activation. T cells appear to lose the ability to form stable synapses after 24 h, but this loss has not been explained satisfactorily. Zacarias Garcia et al. show that T cells can form stable contacts with DCs for at least 48 h, but as increasing numbers of T cells compete for a limited quantity of antigen, expansion is self-limiting. The authors injected mice with T cells and DCs and observed long-lasting conjugates, even though the T cells had previously been activated. The stability of the contacts decreased with the number of T cells injected, although fluorescence microscopy revealed that this reduction was not due to a lack of accessible surface area on the DCs. A pulse of new antigen at 48 h restored the ability of T cells to form synapses. The authors propose that, because full T cell activation requires multiple contacts with DCs over several days, the probability that a T cell will be fully activated decreases as clonal expansion progresses. — K.M.
T cells (red) and dendritic cells (green) in lymph nodes.
“Competition for antigen determines the stability of T cell–dendritic cell interactions during clonal expansion” by Zacarias Garcia, Emmanuelle Pradelli, Susanna Celli, Hélène Beuneu, Aurélie Simon, and Philippe Bousso (see pages 4553–4558)
NEUROSCIENCE
Some prions fail infectivity test
The infective nature of prions, proteins associated with transmissible spongiform encephalopathies such as “mad cow” disease, has been debated since the proteins were first described. Abnormally folded clumps of prion proteins (PrPs) accumulate in the brain, forming diffuse deposits or amyloid plaques that are considered diagnostic markers of prion disease. The association between these abnormal forms of PrP and transmissible disease is not fully understood. Pedro Piccardo et al. inoculated transgenic mice with brain extracts from two human cases of Gerstmann–Sträussler–Scheinker P102L disease, a familial prion disease linked to mutations in the PrP gene. Brain extracts isolated from a patient with spongiform degeneration successfully transmitted a spongiform encephalopathy to the mice. Extracts from a patient without spongiform degeneration, however, resulted in inefficient transmission of disease but significant accumulation of PrP-amyloid. When brain extracts from mice with PrP-amyloid and no spongiform encephalopathy were passaged a second time, PrP-amyloid plaques again formed in the absence of spongiform encephalopathy. Because PrP-amyloid can accumulate and induce the production of further PrP-amyloid without causing a spongiform encephalopathy, the presence of PrP-amyloid may not be a reliable diagnostic marker of infectivity, the authors suggest. — M.M.
PrP-immunopositive plaques in transgenic mouse lacking clinical symptoms.
“Accumulation of prion protein in the brain that is not associated with transmissible disease” by Pedro Piccardo, Jean C. Manson, Declan King, Bernardino Ghetti, and Rona M. Barron (see pages 4712–4717)
