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

P. Obeidy, L.A. Ju, S.H. Oehlers, N.S. Zulkhernain, Q. Lee, J.L. Galeano Niño, R.Y.Q. Kwan, S. Tikoo, L.L. Cavanagh, P. Mrass, A.J.L. Cook, S.P. Jackson, M. Biro, B. Roediger, M.K. Sixt, W. Weninger, Immunology and Cell Biology (2019).


Journal Article | Epub ahead of print | English

Scopus indexed
Author
Obeidy, Peyman; Ju, Lining A.; Oehlers, Stefan H.; Zulkhernain, Nursafwana S.; Lee, Quintin; Galeano Niño, Jorge L.; Kwan, Rain Y.Q.; Tikoo, Shweta; Cavanagh, Lois L.; Mrass, Paulus; Cook, Adam J.L.; Jackson, Shaun P.
All
Department
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.
Publishing Year
Date Published
2019-11-07
Journal Title
Immunology and Cell Biology
ISSN
eISSN
IST-REx-ID

Cite this

Obeidy P, Ju LA, Oehlers SH, et al. Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes. Immunology and Cell Biology. 2019. doi:10.1111/imcb.12304
Obeidy, P., Ju, L. A., Oehlers, S. H., Zulkhernain, N. S., Lee, Q., Galeano Niño, J. L., … Weninger, W. (2019). Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes. Immunology and Cell Biology. https://doi.org/10.1111/imcb.12304
Obeidy, Peyman, Lining A. Ju, Stefan H. Oehlers, Nursafwana S. Zulkhernain, Quintin Lee, Jorge L. Galeano Niño, Rain Y.Q. Kwan, et al. “Partial Loss of Actin Nucleator Actin-Related Protein 2/3 Activity Triggers Blebbing in Primary T Lymphocytes.” Immunology and Cell Biology, 2019. https://doi.org/10.1111/imcb.12304.
P. Obeidy et al., “Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes,” Immunology and Cell Biology, 2019.
Obeidy P, Ju LA, Oehlers SH, Zulkhernain NS, Lee Q, Galeano Niño JL, Kwan RYQ, Tikoo S, Cavanagh LL, Mrass P, Cook AJL, Jackson SP, Biro M, Roediger B, Sixt MK, Weninger W. 2019. Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes. Immunology and Cell Biology.
Obeidy, Peyman, et al. “Partial Loss of Actin Nucleator Actin-Related Protein 2/3 Activity Triggers Blebbing in Primary T Lymphocytes.” Immunology and Cell Biology, Wiley, 2019, doi:10.1111/imcb.12304.
All files available under the following license(s):
Copyright Statement:
This Item is protected by copyright and/or related rights. [...]

Link(s) to Main File(s)
Access Level
OA Open Access

Export

Marked Publications

Open Data IST Research Explorer

Sources

PMID: 31698518
PubMed | Europe PMC

Search this title in

Google Scholar