L M Machesky

..The Arp2/3 complex is highly regulated by a number of actin-binding proteins including the haematopoietic-specific protein HS1 and its homologue cortactin. The present study investigates the role of HS1 in platelets using HS1-/- mice...

..These proteins have been characterised as major regulators of lamellipodia formation downstream of Rac activation and as members of large protein complexes...

..Results were compared with phenotypes in patient skeletal muscle fibres and with previous expression studies in fibroblasts and C2C12 myoblasts/myotubes...

..How this multifunctional protein and its close relative ABBA-1 regulate cellular behaviour is still very much an open question...

..MyosinIIa phosphorylation underlies platelet rounding and stress fiber formation...

..In the present study, we report the identification of a novel actin-rich structure, termed an actin nodule, which appears prior to lamellipodia and stress fibre formation...

..Rac mediates actin assembly via Scar/WAVE, a family of scaffolding proteins that direct actin reorganization by relaying signals from Rac to the Arp2/3 complex...

..Thus, MIM-B is unlikely to be a metastasis suppressor but acts as a scaffold protein that interacts with Rac, actin and actin-associated proteins to modulate lamellipodia formation...

..Furthermore, in NIH 3T3 cells, Scar2 and the Arp2/3 complex appear to be involved in the establishment and maintenance of Golgi polarity during directed migration...

..We describe three classes of BAR domains, BAR, N-BAR and F-BAR, providing examples of each discussing and how they function in linking membranes to the actin cytoskeleton in endocytosis...

..Abp1p, a yeast protein involved in endocytosis, and cortactin, a mammalian src substrate, both enhance the ability of the Arp2/3 complex to assemble branched actin filament networks...

..The involvement of Nck in pedestal formation by EPEC highlights the similar strategies adopted by this bacterium and the Vaccinia virus to hijack the host cell's cytoskeleton...

..These results highlight a possible role for fibronectin in supporting thrombus formation...

..Clearly, the complex has a central role in actin cytoskeletal function and will be the subject of much research in the coming years...

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..Lastly, we could not detect actin monomer sequestration by the Ct extension of IRTKS as would be expected with a conventional WH2 motif, but it did interact with actin filaments...

..The interplay between filopodial and lamellipodial protrusions is an area of much interest as it is thought to be a key determinant of how cells make motility choices...

..In this issue, Shimada et al. (2007) reveal the mode of action of the F-BAR domain, which deepens the initial membrane pit that forms during clathrin-mediated endocytosis...

..Similarly, a wide diversity of 'effector molecules' are now implicated in actin-remodelling downstream of these receptors...

..We postulate that MIM-B may be a regulator of actin assembly downstream of tyrosine kinase signalling and that this activity may explain the involvement of MIM in the metastasis of cancer cells...

..This discovery changes our picture of how small GTPases and multiple other signals converge to stimulate actin polymerization and cell motility...

..We conclude that the Arp2/3 complex is a host-cell factor essential for the actin-based motility of L. monocytogenes, suggesting that it plays a pivotal role in regulating the actin cytoskeleton...

..Furthermore, the tyrosine phosphorylation status does not appear to affect the cell morphology and production of filopod-like structures upon expression of IRSp53...

..Emphasis will be placed on recent developments in the field that have furthered our understanding of actin dynamics and cell motility...

..These observations show for the first time that modulation of Scar1 and WASP expression is a component of the differentiation program of myeloid precursors and indicate that WASP and Scar1 have different roles in mature myeloid cells...

..In addition, this study indicates that MTOC and Golgi polarization events are separately controlled...

..Overall, we found a range of defects and behaviors of the mutants in vitro and in cultured cells, paralleling the complexity of actin-based muscle myopathy phenotypes...

..To accomplish this, VWF binds to two distinct platelet receptors: glycoprotein (GP)Ib-IX-V and integrin alpha(IIb)beta3...

..There are no existing cures for congenital myopathies, although improvements can be made to both the standard of living and the life expectancy of the patient through various therapies...

..We hypothesize that N-WASP and Arp2/3 complex are part of a multiprotein assembly important for the generation of dorsal ruffles and that Scar1 and Scar2 are dispensable for this process...

..Our data show for the first time that mammalian cells contain multiple forms of the Arp2/3 complex...

..While myosins have been previously implicated in FcgammaR phagocytosis, to our knowledge, this is the first demonstration of a role for myosin-II in CR phagocytosis...

..Our findings suggest a critical function for NBR1 in the regulation of receptor trafficking and provide a mechanism for down-regulation of signaling by Spred2 via NBR1...

..This study promotes an expanded view of IRSp53 as an actin regulator that integrates scaffolding and effector functions...

..This 'self-amplifying' signalling module involving Tiam1, Rac and the Arp2/3 complex could thus drive actin polymerization at specific sites in cells that are required for dynamic morphological changes...

..The ability of MAPKAPK2 to phosphorylate one isoform of p16-Arc suggests a possible mechanism by which the p38 MAPK cascade regulates remodeling of the actin cytoskeleton...

..They also suggest a role of the Arp2/3 complex and WASP-family in co-ordinating actin polymerisation and integrin function in migrating neutrophils...

..As key proteins are uncovered which regulate the assembly of actin-based structures, these need to be considered in light of whether they represent potential invasion and metastasis proteins...

..It has also become clear that precise regulation of both Scar and WASP activity is of the utmost importance for their physiological functions...

..These data reveal for the first time distinct spatial association patterns between Cdc42 and its key effector proteins controlling cytoskeletal remodeling...

..By linking calcium to ATRA-dependent signaling, our data open new avenues in the understanding of the mechanisms of differentiation-induction therapy of leukemia...

..An SH2-mutated CrkL, which cannot localize at focal adhesions, failed to recruit ASAP1 into focal adhesions. Thus, CrkL appears to be a lynchpin between ASAP1 and peripheral focal adhesions...

..Taken together, these data suggest that the group Ie formins act with profilin to regulate actin polymerization at specific sites associated with the cell membrane...

..Thus, Src may act as an intermediary to regulate the activity of the Arp2/3 complex in response to external stimuli, via modulation of its interaction with WAVE/Scar proteins...

..In conclusion, invadopodia-associated actin comets are a striking example of consistently arising, spontaneous expression of actin-driven propulsion events that also represent a valuable experimental paradigm...

..These data suggest that the 3 WAVE isoforms exhibit common and distinct features and may potentially be involved in the regulation of actin cytoskeleton in platelets...