Caspase-4 has a role in cell division in epithelial cells through actin depolymerization

Kazuhiro Sumida; Tomomitsu Doi; Kunie Obayashi; Yosuke Chiba; Shohei Nagasaka; Noriyoshi Ogino; Koichiro Miyagawa; Ryoko Baba; Hiroyuki Morimoto; Hideki Hara; Takeshi Terabayashi; Toshimasa Ishizaki; Masaru Harada; Motoyoshi Endo

doi:10.1016/j.bbrc.2023.149394

Caspase-4 has a role in cell division in epithelial cells through actin depolymerization

Biochem Biophys Res Commun. 2024 Feb 5:695:149394. doi: 10.1016/j.bbrc.2023.149394. Epub 2023 Dec 19.

Authors

Affiliations

¹ Third Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; Department of Molecular Biology, University of Occupational and Environmental Health, Kitakyushu, Japan.
² Department of Molecular Biology, University of Occupational and Environmental Health, Kitakyushu, Japan.
³ Third Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
⁴ Department of Anatomy, University of Occupational and Environmental Health, Kitakyushu, Japan.
⁵ Department of Infectious Diseases, Division of Microbiology and Immunochemistry, Asahikawa Medical University, Asahikawa, Japan.
⁶ Department of Pharmacology, Faculty of Medicine, Oita University, Yufu, Japan.
⁷ Department of Molecular Biology, University of Occupational and Environmental Health, Kitakyushu, Japan. Electronic address: mendo@med.uoeh-u.ac.jp.

PMID: 38157629
DOI: 10.1016/j.bbrc.2023.149394

Abstract

In addition to its role in pyroptosis and inflammatory cytokine maturation, caspase-4 (CASP4) also contributes to the fusion of phagosomes with lysosomes and cell migration. However, its role in cell division remains elusive. In this study, we demonstrate that CASP4 is indispensable for proper cell division in epithelial cells. Knockout of CASP4 (CASP4 KO) in HepG2 cells led to delayed cell proliferation, increased cell size, and increased multinucleation. In mitosis, CASP4 KO cells showed multipolar spindles, asymmetric spindle positioning, and chromosome segregation errors, ultimately increasing DNA content and chromosome number. We also found that phalloidin, a marker of filamentous actin, increased in CASP4 KO cells owing to suppressed actin depolymerization. Moreover, the levels of actin polymerization-related proteins, including Rho-associated protein kinase1 (ROCK1), LIM kinase1 (LIMK1), and phosphorylated cofilin, significantly increased in CASP4 KO cells. These results suggest that CASP4 contributes to proper cell division through actin depolymerization.

Keywords: Actin; Caspase; Cell division; Cofilin; Mitosis.

MeSH terms

Actin Depolymerizing Factors* / metabolism
Actins* / metabolism
Cell Movement
Epithelial Cells / metabolism
Lim Kinases / genetics
Mitosis
Phosphorylation

Substances

Actins
Actin Depolymerizing Factors
Lim Kinases