Wiskott-Aldrich syndrome protein regulates podosomes in primary human macrophages

被引:346
作者
Linder, S
Nelson, D
Weiss, M
Aepfelbacher, M
机构
[1] Max von Pettenkofer Inst Med Mikrobiol, D-80336 Munich, Germany
[2] Univ Munich, Inst Prophylaxe & Epidemiol Kreislaufkrankheiten, D-80336 Munich, Germany
[3] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA
[4] Univ Munich, Dr Von Haunerschen Kinderspital, Klinikum Innenstadt, D-80337 Munich, Germany
关键词
D O I
10.1073/pnas.96.17.9648
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Wiskott-Aldrich syndrome protein (WASp) is a hematopoietic-specific, multidomain protein whose mutation is responsible for the immunodeficiency disorder Wiskott-Aldrich syndrome. WASp contains a binding motif for the Rho GTPase CDC42Hs as well as verprolin/cofilin-like actin-regulatory domains, but no specific actin structure regulated by CDC 42Bs-WASp has been identified. We found that WASp colocalizes with CDC42Hs and actin in the core of podosomes, a highly dynamic adhesion structure of human blood-derived macrophages, Microinjection of constitutively active V12CDC42Hs or a constitutively active WASp fragment consisting of the verprolin/cofilin-like domains led to the disassemly of podosomes, Conversely, macrophages from patients expressing truncated forms of WASp completely lacked po dosomes, These findings indicate that WASp controls podosome assembly and, in cooperation with CDC42Hs, podosome disassembly in primary human macrophages.
引用
收藏
页码:9648 / 9653
页数:6
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