Cover Image

Granzyme B-induced and caspase 3-dependent cleavage of gelsolin by mouse cytotoxic T cells modifies cytoskeleton dynamics

Granule-associated perforin and granzymes (gzms) are key effector molecules of cytotoxic T lymphocytes (Tc cells) and natural killer cells and play a critical role in the control of intracellular pathogens and cancer. Based on the notion that many gzms, including A, B, C, K, H, and M exhibit cytotox...

Full description

Saved in:
Bibliographic Details
Main Authors: Martin, Praxedis Sina (Author) , Pardo, Julián (Author) , Schill, Natalie (Author) , Jöckel, Lars (Author) , Berg, Matthias (Author) , Froelich, Christopher J. (Author) , Wallich, Reinhard (Author) , Simon, Markus M. (Author)
Format: Article (Journal)
Language:English
Published: 2010
In: The journal of biological chemistry
Year: 2010, Volume: 285, Issue: 24, Pages: 18918-18927
ISSN:1083-351X
DOI:10.1074/jbc.M109.056028
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1074/jbc.M109.056028
Get full text
Author Notes:Praxedis Martin, Julián Pardo, Natalie Schill, Lars Jöckel, Matthias Berg, Christopher J. Froelich, Reinhard Wallich, and Markus M. Simon
Description
Summary:Granule-associated perforin and granzymes (gzms) are key effector molecules of cytotoxic T lymphocytes (Tc cells) and natural killer cells and play a critical role in the control of intracellular pathogens and cancer. Based on the notion that many gzms, including A, B, C, K, H, and M exhibit cytotoxic activity in vitro, all gzms are believed to serve a similar function in vivo. However, more recent evidence supports the concept that gzms are not unidimensional but, rather, possess non-cytotoxic potential, including stimulation of pro-inflammatory cytokines and anti-viral activities. The present study shows that isolated mouse gzmB cleaves the actin-severing mouse protein, cytoplasmic gelsolin (c-gelsolin) in vitro. However, when delivered to intact target cells by ex vivo immune Tc cells, gzmB mediates c-gelsolin proteolysis via activation of caspases 3/7. The NH(2)-terminal c-gelsolin fragment generated by either gzmB or caspase 3 in vitro constitutively severs actin filaments without destroying the target cells. The observation that gzmB secreted by Tc cells initiates a caspase cascade that disintegrates the actin cytoskeleton in target cells suggests that this intracellular process may contribute to anti-viral host defense.
Item Description:Gesehen am 17.05.2021
Physical Description:Online Resource
ISSN:1083-351X
DOI:10.1074/jbc.M109.056028

Similar Items