Review Articles in 2006

Mismatch repair improves the fidelity of DNA replication and affects recombination, DNA-damage signalling, apoptosis and certain cell-type-specific processes of DNA metabolism. Intriguingly, the same system that guards genomic instability on the one hand contributes to cell death on the other.

Studies on yeast vacuole inheritance have identified rules that probably apply to most organelle-inheritance pathways. They have found a partially conserved mechanism for membrane-cargo transport, and shown that the transport complex regulates the destination and timing of vacuole movement.

The NDR protein kinases regulate morphological changes, mitotic exit, cytokinesis, cell proliferation and apoptosis, as well as neuronal growth and differentiation. Combined data from different model organisms now highlight the conserved roles of these kinases in physiology and disease.

The idea that ejaculated spermatozoa 'race' towards the mature egg and compete to fertilize it is no longer thought to be true. Instead, only a small number of spermatozoa are guided towards the egg by specialized mechanisms that include chemotaxis and thermotaxis.

Many genome-scale, or 'omics', data sets are becoming available for various model organisms. Although each of these data types is valuable on its own, further insights into whole systems can be gained through the integration of omics data sets.

The difficulties that are associated with the experimental determination of atomic structures for interacting proteins mean that predictive methods are needed for progress. Such structural details can be used to turn abstract system representations into models that more accurately reflect biological reality.

Recent advances in RNA interference (RNAi)-mediated gene-knockdown technologies have opened up the possibility of large-scale functional discovery in mammalian systems. RNAi screening could help us to delineate the architecture of signalling pathways much faster than by using traditional approaches.

Tissue engineering has opened up the possibility of studying physiological and pathophysiological processesin vitro. The foundation of this technology is a set of design principles for building three-dimensional tissues that are based on the quantitative analyses of cell and tissue behaviour.

Cycles of mechanosensing, mechanotransduction and mechanoresponse regulate cell behaviour and other important cellular responses, such as growth, differentiation and cell death. Nanofabrication and other new technologies have enabled systematic analysis of the mechanisms of mechanosensing and the downstream cellular responses.

Spatial and temporal dynamics of signalling networks control the specificity of cellular responses to receptor stimulation. Computational models now provide insights into the mechanisms that are responsible for signal amplification, as well as the timing, amplitude, duration and spatial distribution of signalling responses.

Prokaryotic mechanosensitive channels function as molecular switches that transduce bilayer deformations into protein motion. These structural rearrangements generate large non-selective pores that result in fast solute and solvent exchange and function as a prokaryotic 'last line of defence' to sudden osmotic challenges.

Epithelial–mesenchymal transition (EMT) is an essential process during morphogenesis. Dissecting the signalling strategies that orchestrate EMT have shown that a complex signalling network, which controls adhesion, motility, survival and differentiation, also regulates the initiation and execution of EMT during embryonic development.

The concept of 'critical nodes' has been used to define the main junctions in physiologically important, complex signalling networks. Several critical nodes of the insulin network have been identified and shown to have important roles in normal physiology and disease states.

Apoptosis is integral to the development of the simple nematode, during which it claims >10% of the somatic cells that are generated. Recent insights into the regulation and execution of apoptosis in this organism will increase our understanding of developmental apoptosis in more complex species.

The MAPK-activated protein kinase (MK) subfamily consists of three structurally related enzymes that function downstream of MAPKs. These kinases are involved in the regulation of actin architecture, cell migration, development, cell-cycle progression and chromatin remodelling as well as mRNA stability and translation.