Review Articles in 2008

Cells are highly complex structures, but where does this complexity come from? Self-organization principles combined with simple physical constraints seem to control organelle size, number, shape and position. These factors then combine to give rise to the overall cell architecture.

The hypothesis that “tumor production is a possible overhealing” has recently been verified in several studies.In vivoanalysis of genes that are involved in tissue repair combined with gene-expression analysis in wounds and tumours have highlighted remarkable similarities between wound healing and cancer.

The ingestion of particles or cells by phagocytosis and of fluids by macropinocytosis requires cup-shaped invaginations of the plasma membrane. Common signalling mechanisms and distinct signalling patterns characterize the different stages of the formation of phagocytic and macropinocytic cups.

ATR kinase and the related ATM kinase have overlapping but non-redundant functions in the DNA-damage response that maintains genome integrity. ATR signals to regulate DNA replication, cell-cycle transitions and DNA repair through the phosphorylation of various substrates.

Cytochromec is primarily known for its function in the mitochondria as a key participant in the life-supporting function of ATP synthesis. Yet, cytochrome calso has a prominent role in apoptotic pathways and participates in non-apoptotic processes during development.

Extensive research over the past 30 years has revealed the involvement of Ras not only in tumorigenesis but also in many developmental disorders. The complexity of the molecular and cell biological mechanisms of action of Ras proteins indicates that much remains to be learnt.

Animal cloning demonstrates that the genome of a differentiated cell can be reprogrammed to support the development of an entire organism and allow the derivation of pluripotent stem cells. Is there a common mechanism for programming and reprogramming developmental states? And what factors are required?

The neural crest is a migratory population of cells that is unique to vertebrate embryos and that forms numerous derivatives, such as melanocytes, peripheral neurons and glia, and the craniofacial skeleton. Formation of the neural crest is mediated through a multimodule gene regulatory network.

Chemotaxis enables immune cells to reach sites of infection, wounds to heal and the formation of embryonic patterns. Recent results have shed light on how cells orientate in chemotactic gradients, the forces that enable pseudopodia projection and the role of the endocytic cycle in movement.

Sterols and sterol derivatives modulate the Hedgehog (Hh) pathway at multiple levels. Progress in understanding Hh signalling will depend on deepening our knowledge of the cell biology of sterol metabolism and trafficking.

Although fusion proteins that function in different membrane-fusion events can be structurally diverse, their functional activities are often similar. Fusion proteins bring the two membranes into sufficiently close proximity and inject energy into the fusion process.

How do septins, GTP-binding proteins, function in a wide range of cellular processes, such as cell division, cytoskeletal organization and membrane remodelling? Electron microscopy and crystallographic studies provide a glimpse into septin-complex assembly that could answer this question.

The small nuclear GTPase Ran controls the directionality of macromolecular transport between the nucleus and the cytoplasm. Ran also has important roles during mitosis and directs nuclear-envelope dynamics, assembly of the mitotic spindle and the timing of cell-cycle transitions.

Filopodia are thin, actin-rich, finger-like structures that are involved in numerous cellular processes, such as cell migration, wound healing, neurite outgrowth and embryonic development. But what are the mechanisms that regulate filopodia formation in distinct cell types?

Asymmetric cell division, which occurs when a mother cell gives rise to two daughter cells with different fates, is crucial for generating diversity during development and for the function of stem cells. Studies in flies and worms have provided important advances for understanding this process.

DNA helicases and translocases have essential roles in nucleic acid metabolism. Processive helicases must translocate along DNA; however, enzyme self assembly and/or interactions with accessory proteins can regulate the separate translocase and helicase activities of some of these enzymes.

Adipose tissue controls whole-body lipid flux, thereby modulating both glucose and lipid homeostasis in humans. Discovery of new targets that regulate fatty acids in adipocytes might lead to therapeutic modalities that can prevent insulin resistance and type 2 diabetes.

Cell death has historically been divided into regulated (apoptotic) and unregulated (necrotic) mechanisms. Emerging evidence, however, suggests that these two categories do not adequately explain all cell death mechanisms. How and why might non-apoptotic, regulated cell death mechanisms have evolved?

How do cytoskeletal components interact to control cellular processes? At the growing microtubule plus ends, microtubule plus-end tracking proteins (+TIPs) regulate different aspects of cell architecture by controlling microtubule dynamics, microtubule interactions with cellular structures and signalling factors, and forces exerted on microtubule networks.

Recent studies have provided insights into the mechanisms of voltage sensing and have identified new voltage-dependent proteins. Characterizing the general features of voltage sensors might lead to the discovery of further membrane proteins that are regulated by voltage.