Molecular mechanism of Ena/VASP-mediated actin-filament elongation

Ena/VASP proteins have important functions in actin-dependent processes. A model for the actin elongation activity of Ena/VASP based on the affinity and saturation state of WH2-domain-mediated actin monomer binding is presented

The Eps8/IRSp53/VASP Network Differentially Controls Actin Capping and Bundling in Filopodia Formation

There is a body of literature that describes the geometry and the physics of filopodia using either stochastic models or partial differential equations and elasticity and coarse-grained theory. Comparatively, there is a paucity of models focusing on the regulation of the network of proteins that control the formation of different actin structures. Using a combination of in-vivo and in-vitro experiments together with a system of ordinary differential equations, we focused on a small number of well-characterized, interacting molecules involved in actin-dependent filopodia formation: the actin remodeler Eps8, whose capping and bundling activities are a function of its ligands, Abi-1 and IRSp53, respectively; VASP and Capping Protein (CP), which exert antagonistic functions in controlling filament elongation. The model emphasizes the essential role of complexes that contain the membrane deforming protein IRSp53, in the process of filopodia initiation. This model accurately accounted for all observations, including a seemingly paradoxical result whereby genetic removal of Eps8 reduced filopodia in HeLa, but increased them in hippocampal neurons, and generated quantitative predictions, which were experimentally verified. The model further permitted us to explain how filopodia are generated in different cellular contexts, depending on the dynamic interaction established by Eps8, IRSp53 and VASP with actin filaments, thus revealing an unexpected plasticity of the signaling network that governs the multifunctional activities of its components in the formation of filopodia

Force-Velocity Measurements of a Few Growing Actin Filaments

The authors propose a new mechanism for actin-based force generation based on results using chains of actin-grafted magnetic colloids

Arp2/3 complex interactions and actin network turnover in lamellipodia

Cell migration is initiated by lamellipodia—membrane-enclosed sheets of cytoplasm containing densely packed actin filament networks. Although the molecular details of network turnover remain obscure, recent work points towards key roles in filament nucleation for Arp2/3 complex and its activator WAVE complex. Here, we combine fluorescence recovery after photobleaching (FRAP) of different lamellipodial components with a new method of data analysis to shed light on the dynamics of actin assembly/disassembly. We show that Arp2/3 complex is incorporated into the network exclusively at the lamellipodium tip, like actin, at sites coincident with WAVE complex accumulation. Capping protein likewise showed a turnover similar to actin and Arp2/3 complex, but was confined to the tip. In contrast, cortactin—another prominent Arp2/3 complex regulator—and ADF/cofilin—previously implicated in driving both filament nucleation and disassembly—were rapidly exchanged throughout the lamellipodium. These results suggest that Arp2/3- and WAVE complex-driven actin filament nucleation at the lamellipodium tip is uncoupled from the activities of both cortactin and cofilin. Network turnover is additionally regulated by the spatially segregated activities of capping protein at the tip and cofilin throughout the mesh

The Late Cretaceous to recent tectonic history of the Pacific Ocean basin

A vast ocean basin has spanned the region between the Americas, Asia and Australasia for well over 100 Myr, represented today by the Pacific Ocean. Its evolution includes a number of plate fragmentation and plate capture events, such as the formation of the Vancouver, Nazca, and Cocos plates from the break-up of the Farallon plate, and the incorporation of the Bellingshausen, Kula, and Aluk (Phoenix) plates, which have been studied individually, but never been synthesised into one coherent model of ocean basin evolution. Previous regional tectonic models of the Pacific typically restrict their scope to either the North or South Pacific, and global kinematic models fail to incorporate some of the complexities in the Pacific plate evolution (e.g. the independent motion of the Bellingshausen and Aluk plates), thereby limiting their usefulness for understanding tectonic events and processes occurring in the Pacific Ocean perimeter. We derive relative plate motions (with 95% uncertainties) for the Pacific-Farallon/Vancouver, Kula-Pacific, Bellingshausen-Pacific, and early Pacific-West Antarctic spreading systems, based on recent data including marine gravity anomalies, well-constrained fracture zone traces and a large compilation of magnetic anomaly identifications. We find our well-constrained relative plate motions result in a good match to the fracture zone traces and magnetic anomaly identifications in both the North and South Pacific. In conjunction with recently published and well-constrained relative plate motions for other Pacific spreading systems (e.g. Aluk-West Antarctic, Pacific-Cocos, recent Pacific-West Antarctic spreading), we explore variations in the age of the oceanic crust, seafloor spreading rates and crustal accretion and find considerable refinements have been made in the central and southern Pacific. Asymmetries in crustal accretion within the overall Pacific basin (where both flanks of the spreading system are preserved) have typically deviated less than 5% from symmetry, and large variations in crustal accretion along the southern East Pacific Rise (i.e. Pacific-Nazca/Farallon spreading) appear to be unique to this spreading corridor. Through a relative plate motion circuit, we explore the implied convergence history along the North and South Americas, where we find that the inclusion of small tectonic plate fragments such as the Aluk plate are critical for reconciling the history of convergence with onshore geological evidence. © 2015 Elsevier B.V.Australian Research Council, M.S.I. Foundatio

Tectonic Reconstructions of the Southernmost Andes and the Scotia Sea During the Opening of the Drake Passage

Study of the tectonic development of the Scotia Sea region started with basic lithological and structural studies of outcrop geology in Tierra del Fuego and the Antarctic Peninsula. To nineteenth- and early twentieth-century geologists, the results of these studies suggested the presence of a submerged orocline running around the margins of the Scotia Sea. Subsequent increases in detailed knowledge about the fragmentary outcrop geology from islands distributed around the margins of the Scotia Sea, and later their interpretation in the light of the plate tectonic paradigm led to large modifications in the hypothesis such that by the present day the concept of oroclinal bending in the region persists only in vestigial form. Of the early comparative lithostratigraphic work in the region, only the likenesses between Jurassic–Cretaceous basin floor and fill sequences in South Georgia and Tierra del Fuego are regarded as strong enough to be useful in plate kinematic reconstruction by permitting the interpretation of those regions’ contiguity in mid-Mesozoic times. Marine and satellite geophysical data sets reveal features of the remaining, submerged, 98 % of the Scotia Sea region between the outcrops. These data enable a more detailed and quantitative approach to the region’s plate kinematics. In contrast to long-used interpretations of the outcrop geology, these data do not prescribe the proximity of South Georgia to Tierra del Fuego in any past period. It is, however, possible to reinterpret the geology of those two regions in terms of the plate kinematic history that the seafloor has preserved

Filopodia: Complex models for simple rods.

Filopodia are prominent cell surface projections filled with bundles of linear actin filaments that drive their protrusion. These structures are considered important sensory organelles, for instance in neuronal growth cones or during the fusion of sheets of epithelial tissues. In addition, they can serve a precursor function in adhesion site or stress fibre formation. Actin filament assembly is essential for filopodia formation and turnover, yet the precise molecular mechanisms of filament nucleation and/or elongation are controversial. Indeed, conflicting reports on the molecular requirements of filopodia initiation have prompted researchers to propose different types and/or alternative or redundant mechanisms mediating this process. However, recent data shed new light on these questions, and they indicate that the balance of a limited set of biochemical activities can determine the structural outcome of a given filopodium. Here we focus on discussing our current view of the relevance of these activities, and attempt to propose a molecular mechanism of filopodia assembly based on a single core machinery