Calpain-1 weakens the nuclear envelope and promotes the release of neutrophil extracellular traps

Singh J, Zlatar L, Munoz Becerra M, Lochnit G, Herrmann I, Pfister F, Janko C, Knopf J, Leppkes M, Schoen J, Munoz LE, Schett G, Herrmann M, Schauer C, Mahajan A (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Cell Communication and Signaling BioMed Central

Book Volume: 22

Article Number: 435

Journal Issue: 1

DOI: 10.1186/s12964-024-01785-6

Abstract

The inducers of neutrophil extracellular trap (NET) formation are heterogeneous and consequently, there is no specific pathway or signature molecule indispensable for NET formation. But certain events such as histone modification, chromatin decondensation, nuclear envelope breakdown, and NET release are ubiquitous. During NET formation, neutrophils drastically rearrange their cytoplasmic, granular and nuclear content. Yet, the exact mechanism for decoding each step during NET formation still remains elusive. Here, we investigated the mechanism of nuclear envelope breakdown during NET formation. Immunofluorescence microscopic evaluation revealed a gradual disintegration of outer nuclear membrane protein nesprin-1 and alterations in nuclear morphology during NET formation. MALDI-TOF analysis of NETs that had been generated by various inducers detected the accumulation of nesprin-1 fragments. This suggests that nesprin-1 degradation occurs before NET release. In the presence of a calpain-1, inhibitor nesprin-1 degradation was decreased in calcium driven NET formation. Microscopic evaluation confirmed that the disintegration of the lamin B receptor (LBR) and the collapse of the actin cytoskeleton occurs in early and later phases of NET release, respectively. We conclude that the calpain-1 degrades nesprin-1, orchestrates the weakening of the nuclear membrane, contributes to LBR disintegration, and promoting DNA release and finally, NETs formation.

Authors with CRIS profile

Jeeshan Singh Department of Medicine 3 – Rheumatology and Immunology Leticija Zlatar Department of Medicine 3 – Rheumatology and Immunology Marco Munoz Becerra Department of Medicine 3 – Rheumatology and Immunology Felix Pfister Department of Otorhinolaryngology – Head and Neck Surgery (HNO-Klinik) Christina Janko Department of Otorhinolaryngology – Head and Neck Surgery (HNO-Klinik) Jasmin Knopf Department of Medicine 3 – Rheumatology and Immunology Moritz Leppkes Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Janina Schoen Department of Medicine 3 – Rheumatology and Immunology Luis Munoz Becerra Department of Medicine 3 – Rheumatology and Immunology Georg Schett Lehrstuhl für Innere Medizin III Martin Herrmann Department of Medicine 3 – Rheumatology and Immunology Christine Schauer Department of Medicine 3 – Rheumatology and Immunology Aparna Mahajan Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Justus-Liebig-Universität Gießen DE Germany (DE)

How to cite

APA:

Singh, J., Zlatar, L., Munoz Becerra, M., Lochnit, G., Herrmann, I., Pfister, F.,... Mahajan, A. (2024). Calpain-1 weakens the nuclear envelope and promotes the release of neutrophil extracellular traps. Cell Communication and Signaling, 22(1). https://doi.org/10.1186/s12964-024-01785-6

MLA:

Singh, Jeeshan, et al. "Calpain-1 weakens the nuclear envelope and promotes the release of neutrophil extracellular traps." Cell Communication and Signaling 22.1 (2024).

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