Faculty Opinions recommendation of Forces generated by lamellipodial actin filament elongation regulate the WAVE complex during cell migration.

2021 ◽  
Author(s):  
Catherine Galbraith
Keyword(s):  
Cell Migration ◽  
Actin Filament ◽  
Wave Complex

Forces generated by lamellipodial actin filament elongation regulate the WAVE complex during cell migration

2021 ◽  
Author(s):  
Amine Mehidi ◽  
Frieda Kage ◽  
Zeynep Karatas ◽  
Maureen Cercy ◽  
Matthias Schaks ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Filament ◽  
Wave Complex

scholarly journals Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo

2013 ◽  
Vol 203 (4) ◽  
pp. 673-689 ◽  
Author(s):  
Ah-Lai Law ◽  
Anne Vehlow ◽  
Maria Kotini ◽  
Lauren Dodgson ◽  
Daniel Soong ◽  
...  
Keyword(s):  
Cell Migration ◽  
Neural Crest ◽  
Neural Crest Cell ◽  
Direct Interaction ◽  
Dependent Manner ◽  
Border Cell ◽  
Promote Cell Migration ◽  
Wave Complex

Cell migration is essential for development, but its deregulation causes metastasis. The Scar/WAVE complex is absolutely required for lamellipodia and is a key effector in cell migration, but its regulation in vivo is enigmatic. Lamellipodin (Lpd) controls lamellipodium formation through an unknown mechanism. Here, we report that Lpd directly binds active Rac, which regulates a direct interaction between Lpd and the Scar/WAVE complex via Abi. Consequently, Lpd controls lamellipodium size, cell migration speed, and persistence via Scar/WAVE in vitro. Moreover, Lpd knockout mice display defective pigmentation because fewer migrating neural crest-derived melanoblasts reach their target during development. Consistently, Lpd regulates mesenchymal neural crest cell migration cell autonomously in Xenopus laevis via the Scar/WAVE complex. Further, Lpd’s Drosophila melanogaster orthologue Pico binds Scar, and both regulate collective epithelial border cell migration. Pico also controls directed cell protrusions of border cell clusters in a Scar-dependent manner. Taken together, Lpd is an essential, evolutionary conserved regulator of the Scar/WAVE complex during cell migration in vivo.

scholarly journals Dia1 and IQGAP1 interact in cell migration and phagocytic cup formation

2007 ◽  
Vol 178 (2) ◽  
pp. 193-200 ◽  
Author(s):  
Dominique T. Brandt ◽  
Sabrina Marion ◽  
Gareth Griffiths ◽  
Takashi Watanabe ◽  
Kozo Kaibuchi ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Filament ◽  
Cell Shape ◽  
Actin Polymerization ◽  
Binding Protein ◽  
Subcellular Location ◽  
Scaffold Protein ◽  
Cellular Location ◽  
Inhibitory Domain ◽  
Migrating Cells

The Diaphanous-related formin Dia1 nucleates actin polymerization, thereby regulating cell shape and motility. Mechanisms that control the cellular location of Dia1 to spatially define actin polymerization are largely unknown. In this study, we identify the cytoskeletal scaffold protein IQGAP1 as a Dia1-binding protein that is necessary for its subcellular location. IQGAP1 interacts with Dia1 through a region within the Diaphanous inhibitory domain after the RhoA-mediated release of Dia1 autoinhibition. Both proteins colocalize at the front of migrating cells but also at the actin-rich phagocytic cup in macrophages. We show that IQGAP1 interaction with Dia1 is required for phagocytosis and phagocytic cup formation. Thus, we identify IQGAP1 as a novel component involved in the regulation of phagocytosis by mediating the localization of the actin filament nucleator Dia1.

scholarly journals The Role of the Scar/WAVE Complex in the Mechanics of Cell Migration

2011 ◽  
Vol 100 (3) ◽  
pp. 441a
Author(s):  
Effie Bastounis ◽  
Ruedi Meili ◽  
Baldomero Alonso-Latorre ◽  
Juan-Carlos del Alamo ◽  
Richard Firtel ◽  
...  
Keyword(s):  
Cell Migration ◽  
Wave Complex

scholarly journals Aqueous Extract ofPaeonia suffruticosaInhibits Migration and Metastasis of Renal Cell Carcinoma Cells via Suppressing VEGFR-3 Pathway

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Shih-Chin Wang ◽  
Sai-Wen Tang ◽  
Sio-Hong Lam ◽  
Chung-Chieh Wang ◽  
Yu-Huei Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Aqueous Extract ◽  
Actin Filament ◽  
Renal Cell ◽  
Chinese Herbs ◽  
Vegf Receptor ◽  
Cytoskeletal Dynamics ◽  
Cell Migration And Proliferation

Renal cell carcinoma (RCC) cells are characterized by strong drug resistance and high metastatic incidence. In this study, the effects of ten kinds of Chinese herbs on RCC cell migration and proliferation were examined. Aqueous extract ofPaeonia suffruticosa(PS-A) exerted strong inhibitory effects on cancer cell migration, mobility, and invasion. The results of mouse xenograft experiments showed that the treatment of PS-A significantly suppressed tumor growth and pulmonary metastasis. We further found that PS-A markedly decreased expression of VEGF receptor-3 (VEGFR-3) and phosphorylation of FAK in RCC cells. Moreover, the activation of Rac-1, a modulator of cytoskeletal dynamics, was remarkably reduced by PS-A. Additionally, PS-A suppressed polymerization of actin filament as demonstrated by confocal microscopy analysis and decreased the ratio of F-actin to G-actin in RCC cells, suggesting that PS-A inhibits RCC cell migration through modulating VEGFR-3/FAK/Rac-1 pathway to disrupt actin filament polymerization. In conclusion, this research elucidates the effects and molecular mechanism for antimigration of PS-A on RCC cells and suggests PS-A to be a therapeutic or adjuvant strategy for the patients with aggressive RCC.

scholarly journals Extracellular Signalling Modulates Scar/WAVE Complex Activity through Abi Phosphorylation

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3485
Author(s):  
Shashi Prakash Singh ◽  
Peter A. Thomason ◽  
Robert H. Insall
Keyword(s):  
Cell Migration ◽  
Environmental Cues ◽  
Complex Activity ◽  
Extracellular Signals ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Environmental Responses ◽  
Cell Substrate Adhesion ◽  
Extracellular Signalling ◽  
Wave Complex

The lamellipodia and pseudopodia of migrating cells are produced and maintained by the Scar/WAVE complex. Thus, actin-based cell migration is largely controlled through regulation of Scar/WAVE. Here, we report that the Abi subunit—but not Scar—is phosphorylated in response to extracellular signalling in Dictyostelium cells. Like Scar, Abi is phosphorylated after the complex has been activated, implying that Abi phosphorylation modulates pseudopodia, rather than causing new ones to be made. Consistent with this, Scar complex mutants that cannot bind Rac are also not phosphorylated. Several environmental cues also affect Abi phosphorylation—cell-substrate adhesion promotes it and increased extracellular osmolarity diminishes it. Both unphosphorylatable and phosphomimetic Abi efficiently rescue the chemotaxis of Abi KO cells and pseudopodia formation, confirming that Abi phosphorylation is not required for activation or inactivation of the Scar/WAVE complex. However, pseudopodia and Scar patches in the cells with unphosphorylatable Abi protrude for longer, altering pseudopod dynamics and cell speed. Dictyostelium, in which Scar and Abi are both unphosphorylatable, can still form pseudopods, but migrate substantially faster. We conclude that extracellular signals and environmental responses modulate cell migration by tuning the behaviour of the Scar/WAVE complex after it has been activated.

scholarly journals CYRI (FAM49) proteins are local inhibitors of Scar/WAVE induced lamellipodia that bind directly to active Rac1

2017 ◽  
Author(s):  
Loic Fort ◽  
Jose Batista ◽  
Peter Thomason ◽  
Heather J. Spence ◽  
Jennifer Greaves ◽  
...  
Keyword(s):  
Cell Migration ◽  
Mathematical Models ◽  
Positive Feedback ◽  
Sequence Similarity ◽  
Living Cells ◽  
Binding Domain ◽  
Common Motif ◽  
Evolutionarily Conserved ◽  
Wave Induced ◽  
Wave Complex

AbstractActin-based protrusions driving cell migration are reinforced through positive feedback, but it is unclear how the cell restricts the eventual size of a protrusion or limits positive signals to cause splitting or retraction. We have identified an evolutionarily conserved regulator of the protrusion machinery, which we name CYRI (CYFIP-related Rac interacting) protein. CYRI shows sequence similarity to the Scar/WAVE complex member CYFIP in a Domain of Unknown Function, DUF1394. CYRI binds specifically to activated Rac1 via a common motif shared with CYFIP, establishing DUF1394 as a new Rac1 binding domain. CYRI-depleted cells have broad, Scar/WAVE-enriched lamellipodia and enhanced Rac1 signaling. Conversely, CYRI overexpression suppresses spreading and dramatically sharpens protrusions into unproductive needles. CYRI proteins use dynamic inhibition of Scar/WAVE induced actin to focus positive protrusion signals and regulate pseudopod complexity. CYRI behaves like a “local inhibitor” predicted and described in widely accepted mathematical models, but not previously identified in living cells.

scholarly journals Nance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration

2020 ◽  
Author(s):  
Ah-Lai Law ◽  
Shamsinar Jalal ◽  
Fuad Mosis ◽  
Tommy Pallett ◽  
Ahmad Guni ◽  
...  
Keyword(s):  
Cell Migration ◽  
Binding Sites ◽  
Leading Edge ◽  
Mesenchymal Cell ◽  
Negative Regulators ◽  
Binding Partner ◽  
Direct Binding ◽  
The Stability ◽  
Wave Complex ◽  
Lamellipodia Formation

AbstractCell migration is important for development and its aberrant regulation contributes to many diseases. The Scar/WAVE complex is essential for Arp2/3 mediated lamellipodia formation during mesenchymal cell migration and several coinciding signals activate it. However, so far, no direct negative regulators are known. We have identified Nance-Horan Syndrome-like 1 protein (NHSL1) as a novel, direct binding partner of the Scar/WAVE complex, which co-localise at protruding lamellipodia. This interaction is mediated by the Abi SH3 domain and two binding sites in NHSL1. Furthermore, active Rac binds to NHSL1 at two regions that mediate leading edge targeting of NHSL1 suggesting that Rac recruits NHSL1. Surprisingly, NHSL1 inhibits cell migration through its interaction with the Scar/WAVE complex. Mechanistically, NHSL1 may reduce cell migration efficiency by impeding Arp2/3 activity, as measured in cells using a novel Arp2/3 FRET-FLIM biosensor, resulting in reduced F-actin content of lamellipodia, and consequently impairing the stability of lamellipodia protrusions.

scholarly journals CYRI-A limits invasive migration through macropinosome formation and integrin uptake regulation

2021 ◽  
Vol 220 (9) ◽  
Author(s):  
Anh Hoang Le ◽  
Tamas Yelland ◽  
Nikki R. Paul ◽  
Loic Fort ◽  
Savvas Nikolaou ◽  
...  
Keyword(s):  
Cell Migration ◽  
Nutrient Uptake ◽  
Actin Polymerization ◽  
Surface Expression ◽  
Receptor Trafficking ◽  
Negative Regulator ◽  
Rac1 Activity ◽  
Enhanced Surface ◽  
Α5β1 Integrin ◽  
Wave Complex

The Scar/WAVE complex drives actin nucleation during cell migration. Interestingly, the same complex is important in forming membrane ruffles during macropinocytosis, a process mediating nutrient uptake and membrane receptor trafficking. Mammalian CYRI-B is a recently described negative regulator of the Scar/WAVE complex by RAC1 sequestration, but its other paralogue, CYRI-A, has not been characterized. Here, we implicate CYRI-A as a key regulator of macropinosome formation and integrin internalization. We find that CYRI-A is transiently recruited to nascent macropinosomes, dependent on PI3K and RAC1 activity. CYRI-A recruitment precedes RAB5A recruitment but follows sharply after RAC1 and actin signaling, consistent with it being a local inhibitor of actin polymerization. Depletion of both CYRI-A and -B results in enhanced surface expression of the α5β1 integrin via reduced internalization. CYRI depletion enhanced migration, invasion, and anchorage-independent growth in 3D. Thus, CYRI-A is a dynamic regulator of macropinocytosis, functioning together with CYRI-B to regulate integrin trafficking.

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