scholarly journals Deterministic actin waves as generators of cell polarization cues

2019 ◽  
Vol 117 (2) ◽  
pp. 826-835 ◽  
Author(s):  
Luiza Stankevicins ◽  
Nicolas Ecker ◽  
Emmanuel Terriac ◽  
Paolo Maiuri ◽  
Rouven Schoppmeyer ◽  
...  

Dendritic cells “patrol” the human body to detect pathogens. In their search, dendritic cells perform a random walk by amoeboid migration. The efficiency of pathogen detection depends on the properties of the random walk. It is not known how the dendritic cells control these properties. Here, we quantify dendritic cell migration under well-defined 2-dimensional confinement and in a 3-dimensional collagen matrix through recording their long-term trajectories. We find 2 different migration states: persistent migration, during which the dendritic cells move along curved paths, and diffusive migration, which is characterized by successive sharp turns. These states exhibit differences in the actin distributions. Our theoretical and experimental analyses indicate that this kind of motion can be generated by spontaneous actin polymerization waves that contribute to dendritic cell polarization and migration. The relative distributions of persistent and diffusive migration can be changed by modification of the molecular actin filament nucleation and assembly rates. Thus, dendritic cells can control their migration patterns and adapt to specific environments. Our study offers an additional perspective on how dendritic cells tune their searches for pathogens.

Author(s):  
Meng Feng ◽  
Shuping Zhou ◽  
Yong Yu ◽  
Qinghong Su ◽  
Xiaofan Li ◽  
...  

Dendritic cells (DCs), a class of antigen-presenting cells, are widely present in tissues and apparatuses of the body, and their ability to migrate is key for the initiation of immune activation and tolerogenic immune responses. The importance of DCs migration for their differentiation, phenotypic states, and immunologic functions has attracted widespread attention. In this review, we discussed and compared the chemokines, membrane molecules, and migration patterns of conventional DCs, plasmocytoid DCs, and recently proposed DC subgroups. We also review the promoters and inhibitors that affect DCs migration, including the hypoxia microenvironment, tumor microenvironment, inflammatory factors, and pathogenic microorganisms. Further understanding of the migration mechanisms and regulatory factors of DC subgroups provides new insights for the treatment of diseases, such as infection, tumors, and vaccine preparation.


Cell Reports ◽  
2020 ◽  
Vol 33 (2) ◽  
pp. 108258
Author(s):  
Erin D. Lucas ◽  
Johnathon B. Schafer ◽  
Jennifer Matsuda ◽  
Madison Kraus ◽  
Matthew A. Burchill ◽  
...  

2006 ◽  
Vol 176 (9) ◽  
pp. 5205-5212 ◽  
Author(s):  
Ulf Yrlid ◽  
Simon W. F. Milling ◽  
Joanna L. Miller ◽  
Sian Cartland ◽  
Christopher D. Jenkins ◽  
...  

2017 ◽  
Vol 27 (7) ◽  
pp. 515-526 ◽  
Author(s):  
Naoyuki Inagaki ◽  
Hiroko Katsuno

2020 ◽  
Author(s):  
Luiza Da Cunha Stankevicins ◽  
M. Reza Shaebani ◽  
Doriane Vesperini ◽  
Marta Urbanska ◽  
Daniel A. D. Flormann ◽  
...  

AbstractDendritic cells use amoeboid migration to pass through confined tissues to reach the lymph nodes, and this homing function is crucial for immune responses. The underlying mechanisms for this type of migration remain unknown. As vimentin intermediate filaments regulate adhesion-dependent migration, we analyzed whether they have a similar effect on amoeboid migration. We show that lack of vimentin impairs amoeboid migration in vitro in confined environments, and blocks lymph-node homing in mice in vivo. Importantly, we show that vimentin-deficient dendritic cells have a lower coupling factor between cell speed and persistence and reduced target search efficiency (e.g., finding a pathogen, or another cell). These data show that the characteristics of vimentin in its dynamic regulation of cell stiffness and load-bearing, and also elastic capacity, appear to explain the coupling between their migratory ability and search efficiency. Taken together, these data show that vimentin provides the specific mechano-dynamics required for dendritic cell migration and for efficient target searching.Summary statementVimentin contributes to the mechanical stiffness of cells required for amoeboid cell migration through confined spaces, and improves cell-search efficiency. Vimentin-deficient cells migrate more slowly and their migration speed is less coupled to persistence compared to control cells.


2020 ◽  
Author(s):  
Xuehua Xu ◽  
Xi Wen ◽  
Smit Bhimani ◽  
Amer Moosa ◽  
Dustin Parsons ◽  
...  

AbstractThe current dogma is that chemoattractants G protein coupled receptors (GPCRs) activate β phospholipase C (PLCβ) while receptor tyrosine kinases (RTKs) activate γ phospholipase C (PLCγ). Here, we show that chemoattractant/GPCR-mediated membrane recruitment of PLCγ2 constitutes GPCR-mediated phospholipase C (PLC) signaling and is essential for neutrophil polarization and migration during GPCR-mediated chemotaxis. In response to a chemoattractant stimulation, cells lacking PLCγ2 (plcg2kd) displayed altered dynamics of diacylglycerol (DAG) production and calcium response; increased Ras/PI3K/Akt activation; elevated GSK3 phosphorylation and cofilin activation; impaired dynamics of actin polymerization; and consequently defects in cell polarization and migration during chemotaxis. At low temperature, neutrophils expressing the gain-of-function mutant of PLCγ2 (Δ686) displayed better chemotaxis than the cells expressing wild-type PLCγ2. The study provides a molecular mechanism for the dysregulated recruitment and activation of neutrophils in cold-induced urticaria in PLCγ2-associated antibody deficiency and immune dysregulation (PLAID) patients bearing gain-of-function mutations of PLCγ2.


2021 ◽  
Vol 12 ◽  
Author(s):  
Lanette Kempers ◽  
Evelien G. G. Sprenkeler ◽  
Abraham C. I. van Steen ◽  
Jaap D. van Buul ◽  
Taco W. Kuijpers

The actin-related protein (ARP) 2/3 complex, essential for organizing and nucleating branched actin filaments, is required for several cellular immune processes, including cell migration and granule exocytosis. Recently, genetic defects in ARPC1B, a subunit of this complex, were reported. Mutations in ARPC1B result in defective ARP2/3-dependent actin filament branching, leading to a combined immunodeficiency with severe inflammation. In vitro, neutrophils of these patients showed defects in actin polymerization and chemotaxis, whereas adhesion was not altered under static conditions. Here we show that under physiological flow conditions human ARPC1B-deficient neutrophils were able to transmigrate through TNF-α-pre-activated endothelial cells with a decreased efficiency and, once transmigrated, showed definite impairment in subendothelial crawling. Furthermore, severe locomotion and migration defects were observed in a 3D collagen matrix and a perfusable vessel-on-a-chip model. These data illustrate that neutrophils employ ARP2/3-independent steps of adhesion strengthening for transmigration but rely on ARP2/3-dependent modes of migration in a more complex multidimensional environment.


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