BioEssays 11/2009doi: 10.1002/bies.200990046pmid: N/A
Cover Photograph: Thermal noise is routine in the molecular world. Unsurprisingly, nature has not only adapted to it but found ways for its utilization. Actin polymerization, as well as many other cellular processes, is not a smooth process of lengthening or shortening of actin filaments but a random process vulnerable to thermal fluctuations. Fluctuation‐driven subunit exchange between monomeric and polymeric actin pools, also called exchange diffusion, indirectly couples energy of ATP hydrolysis by polymeric actin to the energy of actin polymerization. This provides a basis for regulation of actin filament growth by an actin‐binding protein profilin. See the article by Elena Yarmola and Michael Bubb in this issue. The authors wish to thank Reuben Judd from their laboratory, who provided significant help with preparation of the figure.
How depolymerization can promote polymerization: the case of actin and profilinYarmola, Elena G.; Bubb, Michael R.
doi: 10.1002/bies.200900049pmid: 19795407
Rapid polymerization and depolymerization of actin filaments in response to extracellular stimuli is required for normal cell motility and development. Profilin is one of the most important actin‐binding proteins; it regulates actin polymerization and interacts with many cytoskeletal proteins that link actin to extracellular membrane. The molecular mechanism of profilin has been extensively considered and debated in the literature for over two decades. Here we discuss several accepted hypotheses regarding the mechanism of profilin function as well as new recently emerged possibilities. Thermal noise is routine in molecular world and unsurprisingly, nature has found a way to utilize it. An increasing amount of theoretical and experimental research suggests that fluctuation‐based processes play important roles in many cell events. Here we show how a fluctuation‐based process of exchange diffusion is involved in the regulation of actin polymerization.
Catalytic antibodies: balancing between Dr. Jekyll and Mr. HydeBelogurov, Alexey; Kozyr, Arina; Ponomarenko, Natalia; Gabibov, Alexander
doi: 10.1002/bies.200900020pmid: 19795406
The immunoglobulin molecule is a perfect template for the de novo generation of biocatalytic functions. Catalytic antibodies, or abzymes, obtained by the structural mimicking of enzyme active sites have been shown to catalyze numerous chemical reactions. Natural enzyme analogs for some of these reactions have not yet been found or possibly do not exist at all. Nowadays, the dramatic breakthrough in antibody engineering and expression technologies has promoted a considerable expansion of immunoglobulin's medical applications and is offering abzymes a unique chance to become a promising source of high‐precision “catalytic vaccines.” At the same time, the discovery of natural abzymes on the background of autoimmune disease revealed their beneficial and pathogenic roles in the disease progression. Thus, the conflicting Dr. Jekyll and Mr. Hyde protective and destructive essences of catalytic antibodies should be carefully considered in the development of therapeutic abzyme applications.
Stripe formation in the early fly embryo: principles, models, and networksPapatsenko, Dmitri
doi: 10.1002/bies.200900096pmid: 19795410
Early development of animal embryos begins from spatially distributed products of gene expression, i.e., gradients. While maternal and early zygotic genes form broad and/or terminal gradients, their direct targets appear later on as relatively narrow stripes, which foreshadow presumptive germ layers or future segments. Evidently, stripe expression of the zygotic genes is among the key mechanisms of embryo patterning. In this paper, known qualitative and quantitative models for the stripe formation are considered on the example of early embryogenesis of Drosophila. The current model analysis emphasizes the role of spatial information flow in development. Discussion is given on frequent network motifs, pointing to spatial stripe formation solutions.
Flower symmetry evolution: towards understanding the abominable mystery of angiosperm radiationBusch, Andrea; Zachgo, Sabine
doi: 10.1002/bies.200900081pmid: 19847818
Flower symmetry is considered a morphological novelty that contributed significantly to the rapid radiation of the angiosperms, which already puzzled Charles Darwin and prompted him to name this phenomenon an ‘abominable mystery’. In 2009, the bicentenary of Darwin's birth and the 150th anniversary of the publication of his seminal work, ‘On the Origin of Species’, this question can now be more satisfactorily readdressed. Understanding the molecular control of monosymmetry formation in the model species Antirrhinum opened the path for comparative studies with non‐model species revealing modifications of this trait. TCP transcription factors, named after TEOSINTE BRANCHED 1 in maize, CYCLOIDEA in snapdragon and PCF in rice, control flower monosymmetry development and contributed to establishing this trait several times independently in higher angiosperms. The joint advances in evolutionary and developmental plant research, combined in the novel research field named Evo/Devo, aim at elucidating the molecular mechanisms and strategies to unravel the mystery of how this diversity has been generated.
Cancer‐associated neochromosomes: a novel mechanism of oncogenesisGarsed, Dale W.; Holloway, Andrew J.; Thomas, David M.
doi: 10.1002/bies.200800208pmid: 19795405
Malignant tumours are often characterised by significant rearrangement of the genome. This may be visible in the form of a deranged karyotype with both loss and gain of DNA sequences extending from chromosomal regions to whole chromosomes. In several tumour types, however, gross genomic derangements are minimal, and tumour cells contain one or more additional (supernumerary) chromosomes that may be unrecognisable in terms of a single origin. In this review we term such chromosomes cancer‐associated neochromosomes (CaNCs). In the absence of other identified genomic abnormalities, and because the CaNC is a common feature of the cancer type, it is hypothesised that the genetic alterations required for cell transformation are contained within its structure. In this review, we discuss the potential impact of modern genomic technologies on our understanding of the nature and causes of CaNC formation, which is central to several cancer types, exemplified here by well‐differentiated liposarcoma.
Fungal incompatibility: Evolutionary origin in pathogen defense?Paoletti, Mathieu; Saupe, Sven J.
doi: 10.1002/bies.200900085pmid: 19795412
In fungi, cell fusion between genetically unlike individuals triggers a cell death reaction known as the incompatibility reaction. In Podospora anserina, the genes controlling this process belong to a gene family encoding STAND proteins with an N‐terminal cell death effector domain, a central NACHT domain and a C‐terminal WD‐repeat domain. These incompatibility genes are extremely polymorphic, subject to positive Darwinian selection and display a remarkable genetic plasticity allowing for constant diversification of the WD‐repeat domain responsible for recognition of non‐self. Remarkably, the architecture of these proteins is related to pathogen‐recognition receptors ensuring innate immunity in plants and animals. Here, we hypothesize that these P. anserina incompatibility genes could be components of a yet‐unidentified innate immune system of fungi. As already proposed in the case of plant hybrid necrosis or graft rejection in mammals, incompatibility could be a by‐product of pathogen‐driven divergence in host defense genes.