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Related Concept Videos

Caspases01:24

Caspases

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Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
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Actin Filament Depolymerization01:19

Actin Filament Depolymerization

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Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
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The Contractile Ring02:15

The Contractile Ring

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Contractile rings are composed of microfilaments and are responsible for separating the daughter cells during cytokinesis. Contractile ring assembly proceeds along with other cell cycle events; however, very few mechanistic details are known about the timing and coordination of the contractile rings with the cell cycle.
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Determining the Plane of Cell Division02:13

Determining the Plane of Cell Division

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Positioning the cell division plane is a critical step during development and cell differentiation, particularly during mitosis when the plane is essential for determining the size of the two daughter cells. The cell division plane is perpendicular to the plane of chromosome segregation, but different types of organisms have different cell division mechanisms to suit their morphology and function. 
Animal cells
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Cell Motility through Blebbing01:16

Cell Motility through Blebbing

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Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
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Cytoskeletal Coordination in Cell Migration01:32

Cytoskeletal Coordination in Cell Migration

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A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
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Spatiotemporal Analysis of Cytokinetic Events in Fission Yeast
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Caspase-4 has a role in cell division in epithelial cells through actin depolymerization.

Kazuhiro Sumida1, Tomomitsu Doi2, Kunie Obayashi2

  • 1Third Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; Department of Molecular Biology, University of Occupational and Environmental Health, Kitakyushu, Japan.

Biochemical and Biophysical Research Communications
|December 29, 2023
PubMed
Summary

Caspase-4 (CASP4) is essential for cell division. Its absence causes errors in mitosis, affecting cell proliferation and DNA content by disrupting actin dynamics.

Keywords:
ActinCaspaseCell divisionCofilinMitosis

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Caspase-4 (CASP4) is known for roles in pyroptosis, cytokine maturation, phagosome-lysosome fusion, and cell migration.
  • The function of CASP4 in cell division has not been previously elucidated.

Purpose of the Study:

  • To investigate the role of CASP4 in the process of cell division in epithelial cells.

Main Methods:

  • Utilized CRISPR-Cas9 gene editing to create CASP4 knockout (CASP4 KO) HepG2 cells.
  • Analyzed cell proliferation, cell size, and multinucleation.
  • Examined mitotic progression, spindle formation, chromosome segregation, and DNA content.
  • Assessed filamentous actin levels and actin depolymerization using phalloidin staining.
  • Quantified the expression of key actin polymerization-related proteins (ROCK1, LIMK1, p-cofilin).

Main Results:

  • CASP4 KO cells exhibited delayed proliferation, increased cell size, and multinucleation.
  • Mitotic defects in CASP4 KO cells included multipolar spindles, aberrant spindle positioning, and chromosome segregation errors, leading to increased DNA content.
  • Phalloidin staining revealed increased filamentous actin in CASP4 KO cells due to impaired actin depolymerization.
  • Elevated levels of actin polymerization regulators (ROCK1, LIMK1, phosphorylated cofilin) were observed in CASP4 KO cells.

Conclusions:

  • CASP4 plays a critical, previously unrecognized role in ensuring proper cell division.
  • CASP4 regulates cell division by influencing actin depolymerization and maintaining cytoskeletal integrity.
  • Disruption of CASP4 function leads to significant mitotic abnormalities and affects cell proliferation.