Faculty Opinions recommendation of Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells.

2010 ◽  
Author(s):  
Elizabeth Smythe
Keyword(s):  
High Capacity ◽  
Leading Edge ◽  
Endocytic Sorting ◽  
Sorting System ◽  
Migrating Cells

scholarly journals Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells

2010 ◽  
Vol 190 (4) ◽  
pp. 675-691 ◽  
Author(s):  
Mark T. Howes ◽  
Matthew Kirkham ◽  
James Riches ◽  
Katia Cortese ◽  
Piers J. Walser ◽  
...  
Keyword(s):  
High Capacity ◽  
Leading Edge ◽  
Cellular Adhesion ◽  
Endocytic Pathway ◽  
Membrane Turnover ◽  
Major Pathway ◽  
Endocytic Sorting ◽  
And Migration ◽  
Sorting Station ◽  
Migrating Cells

Although the importance of clathrin- and caveolin-independent endocytic pathways has recently emerged, key aspects of these routes remain unknown. Using quantitative ultrastructural approaches, we show that clathrin-independent carriers (CLICs) account for approximately three times the volume internalized by the clathrin-mediated endocytic pathway, forming the major pathway involved in uptake of fluid and bulk membrane in fibroblasts. Electron tomographic analysis of the 3D morphology of the earliest carriers shows that they are multidomain organelles that form a complex sorting station as they mature. Proteomic analysis provides direct links between CLICs, cellular adhesion turnover, and migration. Consistent with this, CLIC-mediated endocytosis of key cargo proteins, CD44 and Thy-1, is polarized at the leading edge of migrating fibroblasts, while transient ablation of CLICs impairs their ability to migrate. These studies provide the first quantitative ultrastructural analysis and molecular characterization of the major endocytic pathway in fibroblasts, a pathway that provides rapid membrane turnover at the leading edge of migrating cells.

scholarly journals Molecular Regulation of Actin Turnover at the Leading Edge of Migrating Cells

2015 ◽  
Vol 108 (2) ◽  
pp. 179a-180a
Author(s):  
Brannon R. McCullough ◽  
David J. Odde
Keyword(s):  
Leading Edge ◽  
Molecular Regulation ◽  
Actin Turnover ◽  
Migrating Cells

scholarly journals Integrin-mediated Protein Kinase A Activation at the Leading Edge of Migrating Cells

2008 ◽  
Vol 19 (11) ◽  
pp. 4930-4941 ◽  
Author(s):  
Chinten J. Lim ◽  
Kristin H. Kain ◽  
Eugene Tkachenko ◽  
Lawrence E. Goldfinger ◽  
Edgar Gutierrez ◽  
...  
Keyword(s):  
Cell Migration ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Leading Edge ◽  
Pi3 Kinase ◽  
Early Event ◽  
Type I ◽  
Cell Protrusion ◽  
Kinase A ◽  
Migrating Cells

cAMP-dependent protein kinase A (PKA) is important in processes requiring localized cell protrusion, such as cell migration and axonal path finding. Here, we used a membrane-targeted PKA biosensor to reveal activation of PKA at the leading edge of migrating cells. Previous studies show that PKA activity promotes protrusion and efficient cell migration. In live migrating cells, membrane-associated PKA activity was highest at the leading edge and required ligation of integrins such as α4β1 or α5β1 and an intact actin cytoskeleton. α4 integrins are type I PKA-specific A-kinase anchoring proteins, and we now find that type I PKA is important for localization of α4β1 integrin-mediated PKA activation at the leading edge. Accumulation of 3′ phosphorylated phosphoinositides [PtdIns(3,4,5)P3] products of phosphatidylinositol 3-kinase (PI3-kinase) is an early event in establishing the directionality of migration; however, polarized PKA activation did not require PI3-kinase activity. Conversely, inhibition of PKA blocked accumulation of a PtdIns(3,4,5)P3-binding protein, the AKT-pleckstrin homology (PH) domain, at the leading edge; hence, PKA is involved in maintaining cell polarity during migration. In sum, we have visualized compartment-specific PKA activation in migrating cells and used it to reveal that adhesion-mediated localized activation of PKA is an early step in directional cell migration.

scholarly journals Scribble, Lgl1, and myosin II form a complex in vivo to promote directed cell migration

2020 ◽  
Vol 31 (20) ◽  
pp. 2234-2248
Author(s):  
Maha Abedrabbo ◽  
Shoshana Ravid
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Myosin Ii ◽  
Leading Edge ◽  
Directed Cell Migration ◽  
Lethal Giant Larvae ◽  
And Migration ◽  
Migrating Cells

Here we show that Scribble (Scrib), Lethal giant larvae 1 (Lgl1), and myosin II form a complex in vivo and colocalize at the cell leading edge of migrating cells, and this colocalization is interdependent. Scrib and Lgl1 are required for proper cell adhesion, polarity, and migration.

Alstom’s Reconditioning Technologies for Film Cooled Single Crystal (SX) Turbine Blading

2012 ◽  
Author(s):  
Harald Peter Kissel ◽  
Hosam Shahin ◽  
Alexander Stankowski ◽  
Guenter Ambrosy ◽  
Hans Bissig
Keyword(s):  
High Capacity ◽  
Leading Edge ◽  
Repair Process ◽  
Market Demand ◽  
Damage Scenarios ◽  
Automated Production ◽  
Validation Criteria ◽  
Blade Tip ◽  
And Performance ◽  
Production Solutions

Increased availability, reliability and performance combined with reduced maintenance costs are key factors for the success of gas turbine users. Alstom reconditioning answers to this market demand by providing advanced and competitive repair techniques and an increasing broad reconditioning portfolio to its customers. This paper focuses on the reconditioning of film cooled SX components used in the GT24 and GT26 fleet and the latest enabling technologies. The general reconditioning strategy is based on a thorough analysis of the accumulated field experience with SX parts and a controlled, step-wise introduction of new techniques. Taking advantage of the broad interdisciplinary OEM product and design know-how, as well as Alstom’s rich engineering experience in advanced reconditioning, state of the art reconditioning processes have been developed for different damage scenarios for components. This would include the most technically challenging SX “heavy” scope reconditioning. This paper gives an overview about the reconditioning sequence for SX components and some of its key process steps. As an example, the crack braze repair process is described in detail and several novel SX welding techniques for crack repairs, blade tip and temperature controlled leading edge wall thickness restoration are shown. This covers different processes such as TIG welding or laser metal forming (LMF) of SX components. During the last few years, highly automated production solutions and innovative production tools have been implemented, which enable high capacity and consistently high quality of reconditioning. After their successful validation and a limited phase of monitored production, these techniques are applied on rotating and stationary SX turbine parts. Validation criteria and the experience gained during the first years of commercial production and operation in the field will be presented.

scholarly journals Mechanistic of Rac and Cdc42 synchronization at the cell edge by ARHGAP39-dependent signaling nodules and the impact on protrusion dynamics

2021 ◽  
Author(s):  
Michael Howell ◽  
Violaine Delorme-Walker ◽  
Christopher Welch ◽  
Ritu Pathak ◽  
Klaus M Hahn ◽  
...  
Keyword(s):  
Cell Invasion ◽  
Src Kinase ◽  
Leading Edge ◽  
Gtpase Activating Protein ◽  
Invasion And Metastasis ◽  
Cell Edge ◽  
Motile Cells ◽  
Myosin X ◽  
The Impact ◽  
Migrating Cells

Compartmentalization of GTPase regulators into signaling nodules dictates the GTPase pathways selected. Rac and Cdc42 are synchronized at the cell edge for effective protrusion in motile cells but how their activity is coordinated remains elusive. Here, we discovered that ARHGAP39, a Rac and Cdc42 GTPase-activating protein, sequentially interacts with WAVE and mDia2 to control Rac/lamellipodia and Cdc42/filopodia protrusions, respectively. Mechanistically, ARHGAP39 binds to WAVE and, upon phosphorylation by Src kinase, inactivates Rac to promote Cdc42-induced filopodia formation. With our optimized FRET biosensor, we detected active Cdc42 at the filopodia tips that controls filopodia extension. ARHGAP39 is transported to filopodia tips by Myosin-X where it binds mDia2 and inactivates Cdc42 leading to filopodia retraction. Failure in lamellipodia to filopodia switch by defective ARHGAP39 impairs cell invasion and metastasis. Our study reveals that compartmentalization of ARHGAP39 within Rac/Cdc42 signaling nodules orchestrates the synchronization of lamellipodia/filopodia crosstalk and highlights the intricate regulation of leading edge dynamics in migrating cells.

scholarly journals The novel RacE-binding protein GflB sharpens Ras activity at the leading edge of migrating cells

2016 ◽  
Vol 27 (10) ◽  
pp. 1596-1605 ◽  
Author(s):  
Hiroshi Senoo ◽  
Huaqing Cai ◽  
Yu Wang ◽  
Hiromi Sesaki ◽  
Miho Iijima
Keyword(s):  
Rho Gtpases ◽  
Rho Gtpase ◽  
Gene Knockout ◽  
Binding Protein ◽  
Affinity Purification ◽  
Leading Edge ◽  
The Novel ◽  
Gradient Sensing ◽  
Signaling Events ◽  
Migrating Cells

Directional sensing, a process in which cells convert an external chemical gradient into internal signaling events, is essential in chemotaxis. We previously showed that a Rho GTPase, RacE, regulates gradient sensing in Dictyostelium cells. Here, using affinity purification and mass spectrometry, we identify a novel RacE-binding protein, GflB, which contains a Ras GEF domain and a Rho GAP domain. Using biochemical and gene knockout approaches, we show that GflB balances the activation of Ras and Rho GTPases, which enables cells to precisely orient signaling events toward higher concentrations of chemoattractants. Furthermore, we find that GflB is located at the leading edge of migrating cells, and this localization is regulated by the actin cytoskeleton and phosphatidylserine. Our findings provide a new molecular mechanism that connects directional sensing and morphological polarization.

scholarly journals Tiam1 interaction with the PAR complex promotes talin-mediated Rac1 activation during polarized cell migration

2012 ◽  
Vol 199 (2) ◽  
pp. 331-345 ◽  
Author(s):  
Shujie Wang ◽  
Takashi Watanabe ◽  
Kenji Matsuzawa ◽  
Akira Katsumi ◽  
Mai Kakeno ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Cell Migration ◽  
Protein Kinase ◽  
Leading Edge ◽  
Cell Spreading ◽  
Kinase C ◽  
Rac1 Activity ◽  
Directional Movement ◽  
And Migration ◽  
Migrating Cells

Migrating cells acquire front-rear polarity with a leading edge and a trailing tail for directional movement. The Rac exchange factor Tiam1 participates in polarized cell migration with the PAR complex of PAR3, PAR6, and atypical protein kinase C. However, it remains largely unknown how Tiam1 is regulated and contributes to the establishment of polarity in migrating cells. We show here that Tiam1 interacts directly with talin, which binds and activates integrins to mediate their signaling. Tiam1 accumulated at adhesions in a manner dependent on talin and the PAR complex. The interactions of talin with Tiam1 and the PAR complex were required for adhesion-induced Rac1 activation, cell spreading, and migration toward integrin substrates. Furthermore, Tiam1 acted with talin to regulate adhesion turnover. Thus, we propose that Tiam1, with the PAR complex, binds to integrins through talin and, together with the PAR complex, thereby regulates Rac1 activity and adhesion turnover for polarized migration.

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