Latest Articles Include:
- Editorial Board
- trends cell biol 21(4):i (2011)
- The Three Musketeers of Autophagy: phosphorylation, ubiquitylation and acetylation
- trends cell biol 21(4):195-201 (2011)
Autophagy is a highly conserved process that allows cells, tissues and organs to survive onslaughts such as nutrient deprivation, inflammation, hypoxia and other stresses. The core component proteins that regulate autophagy are well known, and the formation of a double-membrane structure that encompasses cytosolic cargo, including protein aggregates and organelles, has been intensively studied. However, less is known about the inputs that specifically alter recruitment of these components and how post-translational modifications can influence autophagy flux, or the rate at which autophagy substrates are turned over. We propose that three types of post-translational modifications – phosphorylation, ubiquitylation and acetylation – are crucial for autophagy induction, regulation and fine-tuning, and are influenced by a variety of stimuli. Understanding these novel mechanisms of autophagy regulation will give us deeper insights into this process and potentially open u! p therapeutic avenues.
- Evolutionary origins of STIM1 and STIM2 within ancient Ca2+ signaling systems
- trends cell biol 21(4):202-211 (2011)
Human stromal interaction molecule (STIM) proteins are parts of elaborate eukaryotic Ca2+ signaling systems that include numerous plasma membrane (PM), endoplasmic reticulum (ER), and mitochondrial Ca2+ transporters, channels and regulators. STIM2 and STIM1 function as Ca2+ sensors with different sensitivities for ER Ca2+. They translocate to ER–PM junctions and open PM Orai Ca2+ influx channels when receptor-mediated Ca2+ release lowers ER Ca2+ levels. The resulting increase in cytosolic Ca2+ leads to the activation of numerous Ca2+ effector proteins that in turn regulate differentiation, cell contraction, secretion and other cell functions. In this review, we use an evolutionary perspective to survey molecular activation mechanisms in the Ca2+ signaling system, with a particular focus on regulatory motifs and functions of the two STIM proteins. We discuss the presence and absence of STIM genes in different species, the order of appearance of STIM versus Orai, and t! he evolutionary addition of new signaling domains to STIM proteins.
- Regeneration in plants and animals: dedifferentiation, transdifferentiation, or just differentiation?
- trends cell biol 21(4):212-218 (2011)
The textbooks and literature of plant biology indicate that plant cells are totipotent, and that regeneration occurs via dedifferentiation, by which the cell and its descendents recapitulate earlier stages of development. However, recent work on the generation of callus, a presumed undifferentiated or dedifferentiated and disorganized cellular mass, indicates that the cells of callus are neither, and that callus forms predominantly from a pre-existing population of stem cells. Recent work in animal regeneration, for example in salamander limbs, also indicates that previous assumptions about the extent of dedifferentiation and pluripotency in animals are in need of critical reassessment. We review here some of these data, compare plant and animal regeneration, and argue that the importance of dedifferentiation and plasticity in regenerating systems is due for reevaluation.
- The endoplasmic reticulum and protein trafficking in dendrites and axons
- trends cell biol 21(4):219-227 (2011)
Neurons are highly polarized cells whose dendrites and axons extend long distances from the cell body to form synapses that mediate neuronal communication. The trafficking of membrane lipids and proteins throughout the neuron is essential for the establishment and maintenance of cell morphology and synaptic function. However, the dynamic shape and spatial organization of secretory organelles, and their role in defining neuronal polarity and the composition of synapses, are not well delineated. In particular, the structure and function of the continuous and intricate network of the endoplasmic reticulum (ER) in neurons remain largely unknown. Here we review our current understanding of the ER in dendrites and axons, its contribution to local trafficking of neurotransmitter receptors, and the implications for synaptic plasticity and pathology.
- Proteolytic networks in cancer
- trends cell biol 21(4):228-237 (2011)
Proteases are important for multiple processes during malignant progression, including tumor angiogenesis, invasion and metastasis. Recent evidence reveals that tumor-promoting proteases function as part of an extensive multidirectional network of proteolytic interactions, in contrast to the unidirectional caspase cascade. These networks involve different constituents of the tumor microenvironment and key proteases, such as cathepsin B, urokinase-type plasminogen activator and several matrix metalloproteinases, occupy central nodes for amplifying proteolytic signals passing through the network. The proteolytic network interacts with other important signaling pathways in tumor biology, involving chemokines, cytokines, and kinases. Viewing these proteolytic interactions as a system of activating and inhibiting reactions provides insight into tumor biology and reveals relevant pharmaceutical targets. This review examines recent advances in understanding proteases in cance! r and summarizes how the network of activity is co-opted to promote tumor progression.
- Hedgehog morphogen: from secretion to reception
- trends cell biol 21(4):238-246 (2011)
A major challenge of developmental biology is to understand how cells coordinate developmental behaviors with their neighbors. To achieve this, cells often employ signaling molecules that emanate from a local source and act at a distance on target cells. The Hedgehog morphogen is an essential signaling molecule required for numerous processes during animal development. Emphasizing the importance of this molecule for both growth control and patterning, Hedgehog signaling activity is often deregulated during cancer formation and progression. The secretion and spread of Hedgehog are not passive processes, but require accessory molecules involved in Hedgehog processing, release, spread and reception. In this review, I focus on the factors that are required to control the spread and activity of Hedgehog, highlighting recent data that have shed light on these processes.
- The mammalian actin-binding protein 1 (mAbp1): a novel molecular player in leukocyte biology
- trends cell biol 21(4):247-255 (2011)
The transmittance of force from the actin cytoskeleton via integrins to extracellular ligands is essential for multiple aspects of leukocyte function. In addition, integrins must be efficiently linked to the cytoskeleton in order to resist external forces that act on the cell. Recently, the mammalian actin-binding protein 1 (mAbp1) was identified as a novel adaptor involved in linking adhesion molecules of the β2 integrin family to the actin cytoskeleton, indicating that this protein might have a fundamental impact on leukocyte functions that are associated explicitly with force transmittance; namely, intraluminal adhesion and phagocytosis. Here, we review the current understanding of the molecular and cellular functions of mAbp1 with a focus on its impact in leukocyte biology.