F-actin-rich territories coordinate apoptosome assembly and caspase activation during DNA damage-induced intrinsic apoptosis

被引:0
|
作者
King, Virginia L. [1 ,2 ]
Campellone, Kenneth G. [1 ,2 ,3 ]
机构
[1] Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT 06269 USA
[2] Univ Connecticut, Inst Syst Genom, Storrs, CT 06269 USA
[3] UConn Hlth, Ctr Aging, Farmington, CT 06030 USA
基金
美国国家卫生研究院;
关键词
INTERMEDIATE-FILAMENTS; STRUCTURAL INSIGHTS; ARP2/3; COMPLEX; GELSOLIN; COFACTOR; COFILIN; JMY; REGULATOR; PROTEINS; BINDING;
D O I
暂无
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The actin cytoskeleton is a ubiquitous participant in cellular functions that maintain viability, but how it controls programmed cell death is not well understood. Here we show that in response to DNA damage, human cells form a juxtanuclear F-actin-rich territory that coordinates the organized progression of apoptosome assembly to caspase activation. This cytoskeletal compartment is created by the actin nucleation factors JMY, WHAMM, and the Arp2/3 complex, and it excludes proteins that inhibit JMY and WHAMM activity. Within the territory, mitochondria undergo outer membrane permeabilization and JMY localization overlaps with punctate structures containing the core apoptosome components cytochrome c and Apaf-1. The F-actin-rich area also encompasses initiator caspase-9 and clusters of a cleaved form of executioner caspase-3 but restricts accessibility of the caspase inhibitor XIAP. The clustering and potency of caspase-3 activation are positively regulated by the amount of actin polymerized by JMY and WHAMM. These results indicate that JMY-mediated actin re-organization functions in apoptotic signaling by coupling the biogenesis of apoptosomes to the localized processing of caspases.
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页数:3
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