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Cytoskeletal Coordination in Cell Migration01:32

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A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
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Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
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Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
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Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
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Actin is a family of globular proteins that are highly abundant in eukaryotic cells. It makes up approximately 1-5% of total cell protein concentration. Actin monomers polymerize to form a complex network of polarized filaments, the actin cytoskeleton, that plays a crucial role in many cellular processes, including cell motility, division, endocytosis, and metastasis of cancer cells.
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Myosins are multimeric motor proteins involved in various cellular processes such as migration, adhesion, and proliferation. Myosin II is the most common type in animal cells, which binds and cross-links actin filaments.
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An Endothelial Planar Cell Model for Imaging Immunological Synapse Dynamics
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The Arp2/3 complex binding protein HS1 is required for efficient dendritic cell random migration and force

Amy C Bendell1, Edward K Williamson, Christopher S Chen

  • 1Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA. hammer@seas.upenn.edu.

Integrative Biology : Quantitative Biosciences From Nano to Macro
|July 6, 2017
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Summary

Haematopoietic lineage cell-specific protein 1 (HS1) is crucial for dendritic cell (DC) migration and force generation. Its absence significantly impairs DC motility, highlighting HS1

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Area of Science:

  • Immunology
  • Cell Biology
  • Cytoskeletal Dynamics

Background:

  • Dendritic cell (DC) migration to lymph nodes is vital for adaptive immunity.
  • The actin cytoskeleton is essential for DC migration, but individual molecular roles are unclear.
  • Haematopoietic lineage cell-specific protein 1 (HS1) is a key Arp2/3 complex binding protein.

Purpose of the Study:

  • To investigate the role of HS1 in dendritic cell migration and force generation.
  • To understand the contribution of HS1 to Arp2/3 complex-dependent actin polymerization in DCs.

Main Methods:

  • Quantified random migration of HS1-deficient (HS1-/-) DCs on 2D surfaces.
  • Assessed DC motility and speed.
  • Measured traction forces using micropost array detectors (mPADs).
  • Utilized Arp2/3 complex inhibitors and Wiskott-Aldrich syndrome protein (WASP)-deficient DCs for comparison.

Main Results:

  • HS1-/- DCs exhibited significantly reduced motility and speed compared to wild-type (WT) DCs.
  • Inhibition of Arp2/3 complex or deficiency in WASP recapitulated reduced DC motility.
  • HS1-/- DCs generated substantially less traction force (3.96 nN) than WT DCs (13.76 nN).
  • WASP-deficient DCs showed only a slight reduction in force generation compared to WT DCs.

Conclusions:

  • HS1 is essential for efficient random migration and force generation in dendritic cells.
  • HS1 and Arp2/3 complex-mediated actin polymerization are critical for optimal DC function.
  • HS1 plays a significant role in DC migration independent of WASP's direct Arp2/3 activation.