scholarly journals Late endosomes promote microglia migration via cytosolic translocation of immature protease cathD

2020 ◽  
Vol 6 (50) ◽  
pp. eaba5783
Author(s):  
Yi-Jun Liu ◽  
Ting Zhang ◽  
Daxiao Cheng ◽  
Junhua Yang ◽  
Sicong Chen ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Adenosine Triphosphate ◽  
Actin Filaments ◽  
Cathepsin D ◽  
Leading Edge ◽  
Organelle Transport ◽  
Actin Monomer ◽  
Late Endosomes ◽  
Cytoskeletal Dynamics ◽  
Cytoskeleton Remodeling

Organelle transport requires dynamic cytoskeleton remodeling, but whether cytoskeletal dynamics are, in turn, regulated by organelles remains elusive. Here, we demonstrate that late endosomes, a type of prelysosomal organelles, facilitate actin-cytoskeleton remodeling via cytosolic translocation of immature protease cathepsin D (cathD) during microglia migration. After cytosolic translocation, late endosome–derived cathD juxtaposes actin filaments at the leading edge of lamellipodia. Suppressing cathD expression or blocking its cytosolic translocation impairs the maintenance but not the initiation of lamellipodial extension. Moreover, immature cathD balances the activity of the actin-severing protein cofilin to maintain globular-actin (G-actin) monomer pool for local actin recycling. Our study identifies cathD as a key lysosomal molecule that unconventionally contributes to actin cytoskeleton remodeling via cytosolic translocation during adenosine triphosphate–evoked microglia migration.

scholarly journals Mechanism of synergistic actin filament pointed end depolymerization by cyclase-associated protein and cofilin

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Tommi Kotila ◽  
Hugo Wioland ◽  
Giray Enkavi ◽  
Konstantin Kogan ◽  
Ilpo Vattulainen ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Actin Filament ◽  
Actin Filaments ◽  
Monomeric Form ◽  
Actin Monomer ◽  
Filament Assembly ◽  
Structural Work ◽  
Cytoskeletal Dynamics ◽  
Pointed End ◽  
Dependent Processes

AbstractThe ability of cells to generate forces through actin filament turnover was an early adaptation in evolution. While much is known about how actin filaments grow, mechanisms of their disassembly are incompletely understood. The best-characterized actin disassembly factors are the cofilin family proteins, which increase cytoskeletal dynamics by severing actin filaments. However, the mechanism by which severed actin filaments are recycled back to monomeric form has remained enigmatic. We report that cyclase-associated-protein (CAP) works in synergy with cofilin to accelerate actin filament depolymerization by nearly 100-fold. Structural work uncovers the molecular mechanism by which CAP interacts with actin filament pointed end to destabilize the interface between terminal actin subunits, and subsequently recycles the newly-depolymerized actin monomer for the next round of filament assembly. These findings establish CAP as a molecular machine promoting rapid actin filament depolymerization and monomer recycling, and explain why CAP is critical for actin-dependent processes in all eukaryotes.

scholarly journals Actin dynamics in living mammalian cells

1998 ◽  
Vol 111 (12) ◽  
pp. 1649-1658 ◽  
Author(s):  
C. Ballestrem ◽  
B. Wehrle-Haller ◽  
B.A. Imhof
Keyword(s):  
Actin Cytoskeleton ◽  
Mammalian Cells ◽  
Fluorescent Protein ◽  
Leading Edge ◽  
Time Lapse ◽  
Living Cells ◽  
Actin Dynamics ◽  
Mammalian Cell Lines ◽  
Cytoskeletal Dynamics ◽  
Green Fluorescent

The actin cytoskeleton maintains the cellular architecture and mediates cell movements. To explore actin cytoskeletal dynamics, the enhanced green fluorescent protein (EGFP) was fused to human β-actin. The fusion protein was incorporated into actin fibers which became depolymerized upon cytochalasin B treatment. This functional EGFP-actin construct enabled observation of the actin cytoskeleton in living cells by time lapse fluorescence microscopy. Stable expression of the construct was obtained in mammalian cell lines of different tissue origins. In stationary cells, actin rich, ring-like structured ‘actin clouds’ were observed in addition to stress fibers. These ruffle-like structures were found to be involved in the reorganization of the actin cytoskeleton. In migratory cells, EGFP-actin was found in the advancing lamellipodium. Immobile actin spots developed in the lamellipodium and thin actin fibers formed parallel to the leading edge. Thus EGFP-actin expressed in living cells unveiled structures involved in the dynamics of the actin cytoskeleton.

scholarly journals The structural basis of actin filament branching by the Arp2/3 complex

2008 ◽  
Vol 180 (5) ◽  
pp. 887-895 ◽  
Author(s):  
Isabelle Rouiller ◽  
Xiao-Ping Xu ◽  
Kurt J. Amann ◽  
Coumaran Egile ◽  
Stephan Nickell ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Actin Filaments ◽  
Electron Tomography ◽  
Leading Edge ◽  
Structural Basis ◽  
Actin Monomer ◽  
Related Protein ◽  
Cooperative Interactions ◽  
Motile Cells ◽  
Branch Formation

The actin-related protein 2/3 (Arp2/3) complex mediates the formation of branched actin filaments at the leading edge of motile cells and in the comet tails moving certain intracellular pathogens. Crystal structures of the Arp2/3 complex are available, but the architecture of the junction formed by the Arp2/3 complex at the base of the branch was not known. In this study, we use electron tomography to reconstruct the branch junction with sufficient resolution to show how the Arp2/3 complex interacts with the mother filament. Our analysis reveals conformational changes in both the mother filament and Arp2/3 complex upon branch formation. The Arp2 and Arp3 subunits reorganize into a dimer, providing a short-pitch template for elongation of the daughter filament. Two subunits of the mother filament undergo conformational changes that increase stability of the branch. These data provide a rationale for why branch formation requires cooperative interactions among the Arp2/3 complex, nucleation-promoting factors, an actin monomer, and the mother filament.

scholarly journals Control of the Actin Cytoskeleton Within Apical and Subapical Regions of Pollen Tubes

2020 ◽  
Vol 8 ◽  
Author(s):  
Yanan Xu ◽  
Shanjin Huang
Keyword(s):  
Pollen Tube ◽  
Actin Cytoskeleton ◽  
Actin Filaments ◽  
Live Cell Imaging ◽  
Spatial Organization ◽  
Molecular Mechanisms ◽  
Actin Binding ◽  
Cytoskeleton Remodeling ◽  
Made In

In flowering plants, sexual reproduction involves a double fertilization event, which is facilitated by the delivery of two non-motile sperm cells to the ovule by the pollen tube. Pollen tube growth occurs exclusively at the tip and is extremely rapid. It strictly depends on an intact actin cytoskeleton, and is therefore an excellent model for uncovering the molecular mechanisms underlying dynamic actin cytoskeleton remodeling. There has been a long-term debate about the organization and dynamics of actin filaments within the apical and subapical regions of pollen tube tips. By combining state-of-the-art live-cell imaging with the usage of mutants which lack different actin-binding proteins, our understanding of the origin, spatial organization, dynamics and regulation of actin filaments within the pollen tube tip has greatly improved. In this review article, we will summarize the progress made in this area.

scholarly journals cAMP bursts control T cell directionality by actin cytoskeleton remodeling

2020 ◽  
Author(s):  
Morgane Simao ◽  
Fabienne Régnier ◽  
Sarah Taheraly ◽  
Achille Fraisse ◽  
Rachida Tacine ◽  
...  
Keyword(s):  
T Cell ◽  
Actin Cytoskeleton ◽  
T Lymphocyte ◽  
Physical Environment ◽  
Cell Imaging ◽  
Morphological Changes ◽  
Leading Edge ◽  
Lymphocyte Migration ◽  
Dynamic Cell ◽  
Cytoskeleton Remodeling

AbstractT lymphocyte migration is an essential step to mounting an efficient immune response. The rapid and random motility of these cells which favors their sentinel role is conditioned by chemokines as well as by the physical environment. Morphological changes, underlaid by dynamic actin cytoskeleton remodeling, are observed throughout migration but especially when the cell modifies its trajectory. Using dynamic cell imaging, we investigated the signaling pathways involved in T cell directionality control. We monitored cAMP variation concomitantly with actin distribution upon T lymphocyte migration and highlighted the fact that spontaneous bursts in cAMP starting from the leading edge, are sufficient to promote stable actin redistribution triggering trajectory modification.

scholarly journals Membrane tension controls adhesion positioning at the leading edge of cells

2017 ◽  
Vol 216 (9) ◽  
pp. 2959-2977 ◽  
Author(s):  
Bruno Pontes ◽  
Pascale Monzo ◽  
Laurent Gole ◽  
Anabel-Lise Le Roux ◽  
Anita Joanna Kosmalska ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Myosin Ii ◽  
Leading Edge ◽  
Membrane Tension ◽  
Independent Manner ◽  
Mechanical Signal ◽  
Cytoskeleton Remodeling ◽  
Upstream Control

Cell migration is dependent on adhesion dynamics and actin cytoskeleton remodeling at the leading edge. These events may be physically constrained by the plasma membrane. Here, we show that the mechanical signal produced by an increase in plasma membrane tension triggers the positioning of new rows of adhesions at the leading edge. During protrusion, as membrane tension increases, velocity slows, and the lamellipodium buckles upward in a myosin II–independent manner. The buckling occurs between the front of the lamellipodium, where nascent adhesions are positioned in rows, and the base of the lamellipodium, where a vinculin-dependent clutch couples actin to previously positioned adhesions. As membrane tension decreases, protrusion resumes and buckling disappears, until the next cycle. We propose that the mechanical signal of membrane tension exerts upstream control in mechanotransduction by periodically compressing and relaxing the lamellipodium, leading to the positioning of adhesions at the leading edge of cells.

Sign in / Sign up

Export Citation Format

Share Document