Latest Articles Include:
- Contents page + Editorial Board
- trends cell biol 20(11):i (2010)
- Corrigendum: Acidic calcium stores open for business: expanding the potential for intracellular Ca2+ signaling: [Trends in Cell Biology 20 (2010), 277–286]
- trends cell biol 20(11):627 (2010)
- Dicing with dogma: de-branching the lamellipodium
- trends cell biol 20(11):628-633 (2010)
The primary event in the movement of a migrating eukaryotic cell is the extension of cytoplasmic sheets termed lamellipodia composed of networks of actin filaments. Lamellipodia networks are thought to arise through the branching of new filaments from the sides of old filaments, producing a dendritic array. Recent studies by electron tomography have revealed the three dimensional organization of lamellipodia and show, contrary to previous evidence, that actin filaments do not form dendritic arrays in vivo. These findings signal a reconsideration of the structural basis of protrusion and about the roles of the different actin nucleating and elongating complexes involved in the process.
- Timing control in regulatory networks by multisite protein modifications
- trends cell biol 20(11):634-641 (2010)
Computational and experimental studies have yielded quantitative insights into the role for multisite phosphorylation, and other protein modifications, in cell function. This work has emphasized the creation of thresholds and switches for cellular decisions. To date, the dynamics of phosphorylation events have been disregarded yet could be equally relevant for cell function. Here, we discuss theoretical predictions about the kinetic functions of multisite phosphorylation in regulatory networks and how these predictions relate to experimental findings. Using DNA replication as an example, we demonstrate that multisite phosphorylations can support coherent origin firing and robustness against rereplication. We suggest that multisite protein modifications provide a molecular mechanism to robustly time cellular events in the cell cycle, the circadian clock and signal transduction.
- Divide and ProsPer: The emerging role of PtdIns3P in cytokinesis
- trends cell biol 20(11):642-649 (2010)
Cytokinesis is the final step of cell division whereby the dividing cells separate physically. Failure of this process has been proposed to cause tumourigenesis. Several specific lipids are essential for cytokinesis, and recent evidence has revealed that phosphatidylinositol 3-phosphate (PtdIns3P) — a well-known regulator of endosomal trafficking, receptor signaling, nutrient sensing and autophagy — plays an evolutionarily conserved role during cytokinesis. The emerging picture is that PtdIns3P and its regulators and effectors constitute a novel regulatory mechanism for cytokinesis. Elucidating the role of PtdIns3P in cytokinesis might contribute to insight into mechanisms of tumour development and suppression.
- WASH, WHAMM and JMY: regulation of Arp2/3 complex and beyond
- trends cell biol 20(11):650-661 (2010)
Arp2/3 complex mediates the nucleation of actin filaments in multiple subcellular processes, and is activated by nucleation-promoting factors (NPFs) from the Wiskott–Aldrich Syndrome family. In exciting new developments, this family has grown by three members: WASH, WHAMM and JMY, which extend the repertoire of dynamic membrane structures that are remodeled following Arp2/3 activation in vivo. These novel NPFs share an actin- and Arp2/3-interacting WCA module, and combine Arp2/3 activation with additional biochemical functions, including capping protein inhibition, microtubule engagement or Arp2/3-independent actin nucleation, none of which had been previously associated with canonical WCA-harboring proteins. Uncovering the physiological relevance of these unique activities will require concerted efforts from multiple disciplines, and is sure to impact our understanding of how the cytoskeleton controls so many dynamic subcellular events.
- Histone demethylases in development and disease
- trends cell biol 20(11):662-671 (2010)
Histone modifications serve as regulatory marks that are instrumental for the control of transcription and chromatin architecture. Strict regulation of gene expression patterns is crucial during development and differentiation, where diverse cell types evolve from common predecessors. Since the first histone lysine demethylase was discovered in 2004, a number of demethylases have been identified and implicated in the control of gene expression programmes and cell fate decisions. Histone demethylases are now emerging as important players in developmental processes and have been linked to human diseases such as neurological disorders and cancer.
- In control at the ER: PTP1B and the down-regulation of RTKs by dephosphorylation and endocytosis
- trends cell biol 20(11):672-679 (2010)
Receptor tyrosine kinases (RTKs) control the cellular response to a range of stimuli by binding extracellular factors and transmitting appropriate signals to intracellular sites. Protein tyrosine phosphatase 1B (PTP1B) modulates the activity of several RTKs by directly targeting the phosphorylated tyrosine residues that dictate their signaling output. Interestingly, the phenotypes of PTP1B deficiency in different contexts point to a more complex role in regulating RTK signaling. Exciting recent results indicate that the endocytic down-regulation of RTKs could be directly controlled by PTP1B. Microscopy studies have demonstrated an effect of PTP1B on post-endocytic internalization of RTKs into multivesicular bodies, and specific substrates that could influence their endosomal trafficking have been identified. These findings reveal a novel link between two important mechanisms of RTK signal attenuation and highlight the multifaceted impact of PTP1B on cell signaling.
- Cell cholesterol homeostasis: Mediation by active cholesterol
- trends cell biol 20(11):680-687 (2010)
Recent evidence suggests that the major pathways mediating cell cholesterol homeostasis respond to a common signal: active membrane cholesterol. Active cholesterol is the fraction that exceeds the complexing capacity of the polar bilayer lipids. Increments in plasma membrane cholesterol exceeding this threshold have an elevated chemical activity (escape tendency) and redistribute via diverse transport proteins to both circulating plasma lipoproteins and intracellular organelles. Active cholesterol thereby prompts several feedback responses. It is the substrate for its own esterification and for the synthesis of regulatory side-chain oxysterols. It also stimulates manifold pathways that down-regulate the biosynthesis, curtail the ingestion and increase the export of cholesterol. Thus, the abundance of cell cholesterol is tightly coupled to that of its polar lipid partners through active cholesterol.