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Cited by 64Cellular Mechanics and InteractionsT-cell and B-cell ImmunologyImmunodeficiency and Autoimmune Disorders

Actin Dynamics at the T Cell Synapse as Revealed by Immune-Related Actinopathies

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Dupré, Loïc, Boztug, Kaan, Pfajfer, Laurène·2021·Frontiers in Cell and Developmental Biology
DOI 10.3389/fcell.2021.665519PMC PMC8266300
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Abstract

The actin cytoskeleton is composed of dynamic filament networks that build adaptable local architectures to sustain nearly all cellular activities in response to a myriad of stimuli. Although the function of numerous players that tune actin remodeling is known, the coordinated molecular orchestration of the actin cytoskeleton to guide cellular decisions is still ill defined. T lymphocytes provide a prototypical example of how a complex program of actin cytoskeleton remodeling sustains the spatio-temporal control of key cellular activities, namely antigen scanning and sensing, as well as polarized delivery of effector molecules, via the immunological synapse. We here review the unique knowledge on actin dynamics at the T lymphocyte synapse gained through the study of primary immunodeficiences caused by mutations in genes encoding actin regulatory proteins. Beyond the specific roles of individual actin remodelers, we further develop the view that these operate in a coordinated manner and are an integral part of multiple signaling pathways in T lymphocytes.

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  • ARP2/3-mediated actin polymerization drives cell spreading at immunological synapses and shapes the complex architectures that enable efficient antigen presentation and lymphocyte activation.

    “ARP2/3-mediated actin polymerization drives cell spreading at immunological synapses and shapes the complex architectures that enable efficient antigen presentation and lymphocyte activation (Fig. 1e) [12, 22, 23].”

    From HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions (2022) · cites this paper as [22]

    The section on cellular-scale synapse control says actin polymerization sustains T-cell spreading over an antigen-presenting cell. The section on ARPC1B deficiency links Arp2/3 to lamellipodial architecture, synapse assembly, and T-cell function. These passages support the spreading, architecture, and lymphocyte-activation aspects, but do not establish that Arp2/3-mediated T-cell actin dynamics makes antigen presentation itself more efficient. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • HEM1-deficient T cells fail to properly integrate antigen signals and fully activate because T cell immune synapses are highly dependent on ARP2/3-mediated F-actin polymerization.

    “Because T cell immune synapses are highly dependent on ARP2/3-mediated F-actin polymerization [12, 22, 23, 37], HEM1-deficient T cells fail to properly integrate antigen signals and fully activate.”

    From HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions (2022) · cites this paper as [22]

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Cited by

Sorted by citations

Authors
Dupré, L., Boztug, K., & Pfajfer, L.
Affiliations
Centre National de la Recherche Scientifique (FR)
ORCID
Pfajfer, Laurène
Venue
Frontiers in Cell and Developmental Biology
Publisher
Frontiers Media SA
Published
2021-06-24
Volume
9
Pages
665519-665519
ISSN
2296-634X (ISSN-L)
DOI
10.3389/fcell.2021.665519
PMC
PMC8266300
OpenAlex
W3174382978
Cited by
64
References
0
Citations by year
2026: 12 · 2025: 7 · 2024: 23 · 2023: 9 · 2022: 11 · 2021: 2
FWCI
1.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Cell and Developmental Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Vienna Science and Technology Fund
  • Centre National de la Recherche Scientifique
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
Keywords
actin cytoskeleton, immunological synapse, T cells, actinopathy, primary immunodeficiency, actin cytoskeleton remodeling, actin regulatory proteins, antigen recognition, T cell polarization, signaling pathways

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