Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis

S Kothakota, T Azuma, C Reinhard, A Klippel, J Tang… - Science, 1997 - science.org
S Kothakota, T Azuma, C Reinhard, A Klippel, J Tang, K Chu, TJ McGarry, MW Kirschner
Science, 1997science.org
The caspase-3 (CPP32, apopain, YAMA) family of cysteinyl proteases has been implicated
as key mediators of apoptosis in mammalian cells. Gelsolin was identified as a substrate for
caspase-3 by screening the translation products of small complementary DNA pools for
sensitivity to cleavage by caspase-3. Gelsolin was cleaved in vivo in a caspase-dependent
manner in cells stimulated by Fas. Caspase-cleaved gelsolin severed actin filaments in vitro
in a Ca2+-independent manner. Expression of the gelsolin cleavage product in multiple cell …
The caspase-3 (CPP32, apopain, YAMA) family of cysteinyl proteases has been implicated as key mediators of apoptosis in mammalian cells. Gelsolin was identified as a substrate for caspase-3 by screening the translation products of small complementary DNA pools for sensitivity to cleavage by caspase-3. Gelsolin was cleaved in vivo in a caspase-dependent manner in cells stimulated by Fas. Caspase-cleaved gelsolin severed actin filaments in vitro in a Ca2+-independent manner. Expression of the gelsolin cleavage product in multiple cell types caused the cells to round up, detach from the plate, and undergo nuclear fragmentation. Neutrophils isolated from mice lacking gelsolin had delayed onset of both blebbing and DNA fragmentation, following apoptosis induction, compared with wild-type neutrophils. Thus, cleaved gelsolin may be one physiological effector of morphologic change during apoptosis.
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