Partial loss of actin nucleator actin‐related protein 2/3 activity triggers blebbing in primary T lymphocytes

Partial loss of actin nucleator actin‐related protein 2/3 activity triggers blebbing in primary T lymphocytes.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1111/imcb.12304
Journal or Publication Title: Immunology & Cell Biology
Volume: 98
Number: 2
Page Range: pp. 93-113
Date: 2020
Divisions: Immune Imaging
Depositing User: General Admin
Identification Number: 10.1111/imcb.12304
ISSN: 0818-9641
Date Deposited: 15 Dec 2020 01:09
Abstract:

T lymphocytes utilize amoeboid migration to navigate effectively within complex microenvironments. The precise rearrangement of the actin cytoskeleton required for cellular forward propulsion is mediated by actin regulators, including the actin-related protein 2/3 (Arp2/3) complex, a macromolecular machine that nucleates branched actin filaments at the leading edge. The consequences of modulating Arp2/3 activity on the biophysical properties of the actomyosin cortex and downstream T cell function are incompletely understood. We report that even a moderate decrease of Arp3 levels in T cells profoundly affects actin cortex integrity. Reduction in total F-actin content leads to reduced cortical tension and disrupted lamellipodia formation. Instead, in Arp3-knockdown cells, the motility mode is dominated by blebbing migration characterized by transient, balloon-like protrusions at the leading edge. Although this migration mode seems to be compatible with interstitial migration in three-dimensional environments, diminished locomotion kinetics and impaired cytotoxicity interfere with optimal T cell function. These findings define the importance of finely tuned, Arp2/3-dependent mechanophysical membrane integrity in cytotoxic effector T lymphocyte activities.

© 2019 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.

Creators:
Creators
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Obeidy, Peyman
UNSPECIFIED
Ju, Lining A
UNSPECIFIED
Oehlers, Stefan H
UNSPECIFIED
Zulkhernain, Nursafwana S
UNSPECIFIED
Lee, Quintin
UNSPECIFIED
Galeano Niño, Jorge L
UNSPECIFIED
Kwan, Rain YQ
UNSPECIFIED
Tikoo, Shweta
UNSPECIFIED
Cavanagh, Lois L
UNSPECIFIED
Mrass, Paulus
UNSPECIFIED
Cook, Adam JL
UNSPECIFIED
Jackson, Shaun P
UNSPECIFIED
Biro, Maté
UNSPECIFIED
Roediger, Ben
UNSPECIFIED
Sixt, Michael
UNSPECIFIED
Weninger, Wolfgang
UNSPECIFIED
Last Modified: 15 Dec 2020 01:09
URI: https://eprints.centenary.org.au/id/eprint/121

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