scholarly journals A Leep1 into migration and macropinocytosis

2021 ◽  
Vol 220 (7) ◽  
Author(s):  
Yvette W.H. Koh ◽  
Jennifer L. Stow
Keyword(s):  
Leading Edge ◽  
Actin Organization ◽  
Wave Complex

Actin organization underpins conserved functions at the leading edge of cells. In this issue, Yang et al. (2021. J. Cell Biol.https://doi.org/10.1083/jcb.202010096) characterize Leep1 as a bi-functional regulator of migration and macropinocytosis through PIP3 and the Scar/WAVE complex.

Caldesmon affects actin organization at the leading edge and inhibits cell migration

BIOPHYSICS ◽  
2008 ◽  
Vol 53 (6) ◽  
pp. 527-532
Author(s):  
T. V. Kudryashova ◽  
P. N. Rutkevich ◽  
A. Ya. Shevelev ◽  
T. N. Vlasik ◽  
A. V. Vorotnikov
Keyword(s):  
Cell Migration ◽  
Leading Edge ◽  
Actin Organization

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.

Drosophila RhoA regulates the cytoskeleton and cell-cell adhesion in the developing epidermis

Development ◽  
2002 ◽  
Vol 129 (13) ◽  
pp. 3173-3183 ◽  
Author(s):  
James W. Bloor ◽  
Daniel P. Kiehart
Keyword(s):  
Cell Adhesion ◽  
Leading Edge ◽  
Small Gtpase ◽  
Dominant Negative ◽  
Cell Physiology ◽  
Dorsal Closure ◽  
Adhesive Properties ◽  
Actin Organization ◽  
On Line ◽  
Cell Cell

The small GTPase Rho is a molecular switch that is best known for its role in regulating the actomyosin cytoskeleton. We have investigated its role in the developing Drosophila embryonic epidermis during the process of dorsal closure. By expressing the dominant negative DRhoAN19 construct in stripes of epidermal cells, we confirm that Rho function is required for dorsal closure and demonstrate that it is necessary to maintain the integrity of the ventral epidermis. We show that defects in actin organization, nonmuscle myosin II localization, the regulation of gene transcription, DE-cadherin-based cell-cell adhesion and cell polarity underlie the effects of DRhoAN19 expression. Furthermore, we demonstrate that these changes in cell physiology have a differential effect on the epidermis that is dependent upon position in the dorsoventral axis. In the ventral epidermis, cells either lose their adhesiveness and fall out of the epidermis or undergo apoptosis. At the leading edge, cells show altered adhesive properties such that they form ectopic contacts with other DRhoAN19-expressing cells. Movies available on-line

scholarly journals Xenopus cytoplasmic linker–associated protein 1 (XCLASP1) promotes axon elongation and advance of pioneer microtubules

2013 ◽  
Vol 24 (10) ◽  
pp. 1544-1558 ◽  
Author(s):  
Astrid Marx ◽  
William J. Godinez ◽  
Vasil Tsimashchuk ◽  
Peter Bankhead ◽  
Karl Rohr ◽  
...  
Keyword(s):  
Growth Cone ◽  
Binding Protein ◽  
Leading Edge ◽  
Growth Cones ◽  
Retrograde Flow ◽  
Spinal Cord Neurons ◽  
Actin Organization ◽  
Axon Elongation ◽  
Axon Extension ◽  
Potential Link

Dynamic microtubules (MTs) are required for neuronal guidance, in which axons extend directionally toward their target tissues. We found that depletion of the MT-binding protein Xenopus cytoplasmic linker–associated protein 1 (XCLASP1) or treatment with the MT drug Taxol reduced axon outgrowth in spinal cord neurons. To quantify the dynamic distribution of MTs in axons, we developed an automated algorithm to detect and track MT plus ends that have been fluorescently labeled by end-binding protein 3 (EB3). XCLASP1 depletion reduced MT advance rates in neuronal growth cones, very much like treatment with Taxol, demonstrating a potential link between MT dynamics in the growth cone and axon extension. Automatic tracking of EB3 comets in different compartments revealed that MTs increasingly slowed as they passed from the axon shaft into the growth cone and filopodia. We used speckle microscopy to demonstrate that MTs experience retrograde flow at the leading edge. Microtubule advance in growth cone and filopodia was strongly reduced in XCLASP1-depleted axons as compared with control axons, but actin retrograde flow remained unchanged. Instead, we found that XCLASP1-depleted growth cones lacked lamellipodial actin organization characteristic of protrusion. Lamellipodial architecture depended on XCLASP1 and its capacity to associate with MTs, highlighting the importance of XCLASP1 in actin–microtubule interactions.

scholarly journals CYFIP2 containing WAVE complexes inhibit cell migration

2020 ◽  
Author(s):  
Anna Polesskaya ◽  
Arthur Boutillon ◽  
Yanan Wang ◽  
Marc Lavielle ◽  
Sophie Vacher ◽  
...  
Keyword(s):  
Cell Migration ◽  
Mammary Epithelial Cells ◽  
Leading Edge ◽  
Good Prognosis ◽  
Mammary Epithelial ◽  
Breast Cancer Patients ◽  
Loss Of Function ◽  
A Cell ◽  
Wave Complex

ABSTRACTBranched actin networks polymerized by the Arp2/3 complex are critical for cell migration. The WAVE complex is the major Arp2/3 activator at the leading edge of migrating cells. However, multiple distinct WAVE complexes can be assembled in a cell, due to the combinatorial complexity of paralogous subunits. When systematically analyzing the contribution of each WAVE complex subunit to the metastasis-free survival of breast cancer patients, we found that overexpression of the CYFIP2 subunit was surprisingly associated with good prognosis. Gain and loss of function experiments in transformed and untransformed mammary epithelial cells revealed that cell migration was always inversely related to CYFIP2 levels. The role of CYFIP2 was systematically opposite to the role of the paralogous subunit CYFIP1 or of the NCKAP1 subunit. The specific CYFIP2 function in inhibiting cell migration was related to its unique ability to down-regulate classical pro-migratory WAVE complexes. The anti-migratory function of CYFIP2 was also revealed in migration of prechordal plate cells during gastrulation of the zebrafish embryo, indicating that the unique function of CYFIP2 is critically important in both physiological and pathophysiological migrations.

scholarly journals Analysis of a Lower-Tropospheric Gravity Wave Train Using Direct and Remote Sensing Measurement Systems

2017 ◽  
Vol 145 (7) ◽  
pp. 2791-2812 ◽  
Author(s):  
Benjamin A. Toms ◽  
Jessica M. Tomaszewski ◽  
David D. Turner ◽  
Steven E. Koch
Keyword(s):  
Gravity Wave ◽  
Great Plains ◽  
Wave Train ◽  
Leading Edge ◽  
Relative Difference ◽  
Density Current ◽  
Near Surface ◽  
Hydraulic Theory ◽  
Error Propagation Analysis ◽  
Wave Complex

On 10 August 2014, a gravity wave complex generated by convective outflow propagated across much of Oklahoma. The four-dimensional evolution of the wave complex was analyzed using a synthesis of near-surface and vertical observations from the Oklahoma Mesonet and Atmospheric Radiation Measurement (ARM) Southern Great Plains networks. Two Atmospheric Emitted Radiance Interferometers (AERI)—one located at the ARM SGP central facility in Lamont, Oklahoma, and the other in Norman, Oklahoma—were used in concert with a Doppler wind lidar (DWL) in Norman to determine the vertical characteristics of the wave complex. Hydraulic theory was applied to the AERI-derived observations to corroborate the observationally derived wave characteristics. It was determined that a bore-soliton wave packet initially formed when a density current interacted with a nocturnal surface-based inversion and eventually propagated independently as the density current became diffuse. The soliton propagated within an elevated inversion, which was likely induced by ascending air at the leading edge of the bore head. Bore and density current characteristics derived from the observations agreed with hydraulic theory estimates to within a relative difference of 15%. While the AERI did not accurately resolve the postbore elevated inversion, an error propagation analysis suggested that uncertainties in the AERI and DWL observations had a negligible influence on the findings of this study.

scholarly journals The SCAR/WAVE complex is necessary for proper regulation of traction stresses during amoeboid motility

2011 ◽  
Vol 22 (21) ◽  
pp. 3995-4003 ◽  
Author(s):  
Effie Bastounis ◽  
Ruedi Meili ◽  
Baldomero Alonso-Latorre ◽  
Juan C. del Álamo ◽  
Juan C. Lasheras ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Polymerization ◽  
Leading Edge ◽  
Wild Type ◽  
Amoeboid Motility ◽  
Elastic Substrates ◽  
Random Manner ◽  
Motility Cycle ◽  
Wave Complex

Cell migration requires a tightly regulated, spatiotemporal coordination of underlying biochemical pathways. Crucial to cell migration is SCAR/WAVE–mediated dendritic F-actin polymerization at the cell's leading edge. Our goal is to understand the role the SCAR/WAVE complex plays in the mechanics of amoeboid migration. To this aim, we measured and compared the traction stresses exerted by Dictyostelium cells lacking the SCAR/WAVE complex proteins PIR121 (pirA−) and SCAR (scrA−) with those of wild-type cells while they were migrating on flat, elastic substrates. We found that, compared to wild type, both mutant strains exert traction stresses of different strengths that correlate with their F-actin levels. In agreement with previous studies, we found that wild-type cells migrate by repeating a motility cycle in which the cell length and strain energy exerted by the cells on their substrate vary periodically. Our analysis also revealed that scrA− cells display an altered motility cycle with a longer period and a lower migration velocity, whereas pirA− cells migrate in a random manner without implementing a periodic cycle. We present detailed characterization of the traction-stress phenotypes of the various cell lines, providing new insights into the role of F-actin polymerization in regulating cell–substratum interactions and stresses required for motility.

scholarly journals Leep1 interacts with PIP3 and the Scar/WAVE complex to regulate cell migration and macropinocytosis

2021 ◽  
Vol 220 (7) ◽  
Author(s):  
Yihong Yang ◽  
Dong Li ◽  
Xiaoting Chao ◽  
Shashi P. Singh ◽  
Peter Thomason ◽  
...  
Keyword(s):  
Leading Edge ◽  
Cell Types ◽  
Model System ◽  
Cellular Mechanism ◽  
Leucine Rich Repeat ◽  
Repeat Domain ◽  
Full Complement ◽  
Proteomic Screening ◽  
Spatiotemporal Coordination ◽  
Wave Complex

Polarity is essential for diverse functions in many cell types. Establishing polarity requires targeting a network of specific signaling and cytoskeleton molecules to different subregions of the cell, yet the full complement of polarity regulators and how their activities are integrated over space and time to form morphologically and functionally distinct domains remain to be uncovered. Here, by using the model system Dictyostelium and exploiting the characteristic chemoattractant-stimulated translocation of polarly distributed molecules, we developed a proteomic screening approach, through which we identified a leucine-rich repeat domain–containing protein we named Leep1 as a novel polarity regulator. We combined imaging, biochemical, and phenotypic analyses to demonstrate that Leep1 localizes selectively at the leading edge of cells by binding to PIP3, where it modulates pseudopod and macropinocytic cup dynamics by negatively regulating the Scar/WAVE complex. The spatiotemporal coordination of PIP3 signaling, Leep1, and the Scar/WAVE complex provides a cellular mechanism for organizing protrusive structures at the leading edge.

scholarly journals A single tyrosine phosphorylation site in cortactin is important for filopodia formation in neuronal growth cones

2019 ◽  
Vol 30 (15) ◽  
pp. 1817-1833 ◽  
Author(s):  
Yuan Ren ◽  
Yingpei He ◽  
Sherlene Brown ◽  
Erica Zbornik ◽  
Michael J. Mlodzianoski ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Phosphorylation Site ◽  
Leading Edge ◽  
Growth Cones ◽  
Neuronal Growth ◽  
Src Tyrosine Kinase ◽  
Actin Organization ◽  
Neuronal Growth Cones ◽  
Tyrosine Phosphorylation Site

Cortactin is a Src tyrosine phosphorylation substrate that regulates multiple actin-related cellular processes. While frequently studied in nonneuronal cells, the functions of cortactin in neuronal growth cones are not well understood. We recently reported that cortactin mediates the effects of Src tyrosine kinase in regulating actin organization and dynamics in both lamellipodia and filopodia of Aplysia growth cones. Here, we identified a single cortactin tyrosine phosphorylation site (Y499) to be important for the formation of filopodia. Overexpression of a 499F phospho-deficient cortactin mutant decreased filopodia length and density, whereas overexpression of a 499E phospho-mimetic mutant increased filopodia length. Using an antibody against cortactin pY499, we showed that tyrosine-phosphorylated cortactin is enriched along the leading edge. The leading edge localization of phosphorylated cortactin is Src2-dependent, F-actin–independent, and important for filopodia formation. In vitro kinase assays revealed that Src2 phosphorylates cortactin at Y499, although Y505 is the preferred site in vitro. Finally, we provide evidence that Arp2/3 complex acts downstream of phosphorylated cortactin to regulate density but not length of filopodia. In conclusion, we have characterized a tyrosine phosphorylation site in Aplysia cortactin that plays a major role in the Src/cortactin/Arp2/3 signaling pathway controlling filopodia formation.

scholarly journals Abi Is Required for Modulation and Stability but Not Localization or Activation of the SCAR/WAVE Complex

2013 ◽  
Vol 12 (11) ◽  
pp. 1509-1516 ◽  
Author(s):  
Andrew J. Davidson ◽  
Seiji Ura ◽  
Peter A. Thomason ◽  
Gabriela Kalna ◽  
Robert H. Insall
Keyword(s):  
Cell Separation ◽  
Leading Edge ◽  
Experimental Manipulation ◽  
Exact Role ◽  
Content Type ◽  
Small Complex ◽  
N Terminus ◽  
The Individual ◽  
Wave Complex ◽  
Deletion Series

ABSTRACT The SCAR/WAVE complex drives actin-based protrusion, cell migration, and cell separation during cytokinesis. However, the contribution of the individual complex members to the activity of the whole remains a mystery. This is primarily because complex members depend on one another for stability, which limits the scope for experimental manipulation. Several studies suggest that Abi, a relatively small complex member, connects signaling to SCAR/WAVE complex localization and activation through its polyproline C-terminal tail. We generated a deletion series of the Dictyostelium discoideum Abi to investigate its exact role in regulation of the SCAR complex and identified a minimal fragment that would stabilize the complex. Surprisingly, loss of either the N terminus of Abi or the C-terminal polyproline tail conferred no detectable defect in complex recruitment to the leading edge or the formation of pseudopods. A fragment containing approximately 20% Abi—and none of the sites that couple to known signaling pathways—allowed the SCAR complex to function with normal localization and kinetics. However, expression of N-terminal Abi deletions exacerbated the cytokinesis defect of the Dictyostelium abi mutant, which was earlier shown to be caused by the inappropriate activation of SCAR. This demonstrates, unexpectedly, that Abi does not mediate the SCAR complex's ability to make pseudopods, beyond its role in complex stability. Instead, we propose that Abi has a modulatory role when the SCAR complex is activated through other mechanisms.

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