Hot off the presses! Sep 01 Trends Cell Biol

The Sep 01 issue of the Trends Cell Biol is now up on Pubget (About Trends Cell Biol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Editorial Board
  - Trends Cell Biol 19(9):i (2009)
  
• Intracellular transport by active diffusion
  - Trends Cell Biol 19(9):423-427 (2009)
  All substances exhibit constant random motion at the microscopic scale. This is a direct consequence of thermal agitation, and leads to diffusion of molecules and small particles in a liquid. In addition to this nondirected motion, living cells also use active transport mechanisms, such as motor activity and polymerization forces that depend on linear biopolymers and are therefore fundamentally directed in nature. Nevertheless, it has become increasingly clear that such active processes can also drive significant random fluctuations that can appear surprisingly like thermal diffusion of particles, but faster. Here, we discuss recent progress in quantifying this behavior and identifying its origins and consequences. We suggest that it represents an important and biologically tunable mechanism for transport in living cells.
• Do membrane undulations help cells probe the world?
  - Trends Cell Biol 19(9):428-433 (2009)
  Cells sense physical properties of their environment including substratum rigidity, roughness, and topography of recognition sites. The cell surface displays continuous deformations of nanometer-scale amplitude and Hz frequency. Recent results support the hypothesis that these surface undulations constitute a powerful strategy for the rapid acquisition of environmental cues: transient contact with surroundings generates forces of piconewton intensity as a result of rapid formation and dissociation of intermolecular bonds. The combination of binding and steric forces is expected to drive conformational changes and lateral reorganization of membrane biomolecules, thus generating signaling cascades. We propose that spontaneous membrane mobility shapes the initial information generated by cell-to-surface contacts, and thereby biases later consequences of these interactions.
• Tetraspanin-enriched microdomains: a functional unit in cell plasma membranes
  - Trends Cell Biol 19(9):434-446 (2009)
  Membrane lipids and proteins are non-randomly distributed and are unable to diffuse freely in the plane of the membrane. This is because of multiple constraints imposed both by the cortical cytoskeleton and by the preference of lipids and proteins to cluster into diverse and specialized membrane domains, including tetraspanin-enriched microdomains, glycosylphosphatidyl inositol-linked proteins nanodomains and caveolae, among others. Recent biophysical characterization of tetraspanin-enriched microdomains suggests that they might be specially suited for the regulation of avidity of adhesion receptors and the compartmentalization of enzymatic activities. Moreover, modulation by tetraspanins of the function of adhesion receptors involved in inflammation, lymphocyte activation, cancer and pathogen infection suggests potential as therapeutic targets. This review explores this emerging picture of tetraspanin microdomains and discusses the implications for cell adhesion, prot! eolysis and pathogenesis.
• Microtubule-dependent cell morphogenesis in the fission yeast
  - Trends Cell Biol 19(9):447-454 (2009)
  In many systems, microtubules contribute spatial information to cell morphogenesis, for instance in cell migration and division. In rod-shaped fission yeast cells, microtubules control cell morphogenesis by transporting polarity factors, namely the Tea1–Tea4 complex, to cell tips. This complex then recruits the DYRK kinase Pom1 to cell ends. Interestingly, recent work has shown that these proteins also provide long-range spatial cues to position the division site in the middle of the cell and temporal signals to coordinate cell length with the cell cycle. Here I review how these microtubule-associated proteins form polar morphogenesis centers that control and integrate both spatial and temporal aspects of cell morphogenesis.
• Molecular mechanisms involved in inflammasome activation
  - Trends Cell Biol 19(9):455-464 (2009)
  Germline-encoded pattern recognition receptors (PRRs) sense microbial or endogenous products released from damaged or dying cells and trigger innate immunity. In most cases, sensing of these signals is coupled to signal transduction pathways that lead to transcription of immune response genes that combat infection or lead to cell death. Members of the NOD-like receptor (NLR) family assemble into large multiprotein complexes, termed inflammasomes. Inflammasomes do not regulate transcription of immune response genes, but activate caspase-1, a proteolytic enzyme that cleaves and activates the secreted cytokines interleukin-1β and interleukin-18. Inflammasomes also regulate pyroptosis, a caspase-1-dependent form of cell death that is highly inflammatory. Here, we review exciting recent developments on the role of inflammasome complexes in host defense and the discovery of a new DNA sensing inflammasome, and describe important progress made in our understanding of how infl! ammasomes are activated. Additionally, we highlight how dysregulation of inflammasomes contributes to human disease.
• To localize or not to localize: mRNA fate is in 3′UTR ends
  - Trends Cell Biol 19(9):465-474 (2009)
  Translation of localized mRNA is a fast and efficient way of reacting to extracellular stimuli with the added benefit of providing spatial resolution to the cellular response. The efficacy of this adaptive response ultimately relies on the ability to express a particular protein at the right time and in the right place. Although mRNA localization is a mechanism shared by most organisms, it is especially relevant in highly polarized cells, such as differentiated neurons. 3′-Untranslated regions (3′UTRs) of mRNAs are critical both for the targeting of transcripts to specific subcellular compartments and for translational control. Here we review recent studies that indicate how, in response to extracellular cues, nuclear and cytoplasmic remodeling of the 3′UTR contributes to mRNA localization and local protein synthesis.
• Multi-level molecular clutches in motile cell processes
  - Trends Cell Biol 19(9):475-486 (2009)
  To trigger cell motility, forces generated by the cytoskeleton must be transmitted physically to the external environment through transmembrane adhesion molecules. One model put forward twenty years ago to describe this process is the molecular clutch by which a modular interface of adaptor proteins mediates a dynamic mechanical connection between the actin flow and cell adhesion complexes. Recent optical imaging experiments have identified key clutch molecules linked to specific chemical and mechanical signal transduction pathways, particularly regarding integrins in migrating cells, IgCAMs in neuronal growth cones, and cadherins at intercellular junctions. We propose here the concept of a multi-level clutch as a useful analogy to grasp the complexity of the dynamic molecular interactions involved in a panel of motile behaviors and shapes.