期刊
NATURE CELL BIOLOGY
卷 10, 期 3, 页码 259-U7出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb1688
关键词
-
类别
资金
- Medical Research Council [G0501455(76848), G0501455] Funding Source: Medline
- Wellcome Trust [072005] Funding Source: Medline
- MRC [G0501455] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/E500110/1] Funding Source: researchfish
- Medical Research Council [G0601841B] Funding Source: researchfish
The dynamic regulation of actin polymerization plays crucial roles in cell morphology and endocytosis. The mechanistic details of these processes and the proteins involved are not fully understood, especially in neurons. PICK1 is a PDZ-BAR-domain protein involved in regulated AMPA receptor (AMPAR) endocytosis in neurons. Here, we demonstrate that PICK1 binds filamentous (F)-actin and the actin-nucleating Arp2/3 complex, and potently inhibits Arp2/3-mediated actin polymerization. RNA interference (RNAi) knockdown of PICK1 in neurons induces a reorganization of the actin cytoskeleton resulting in aberrant cell morphology. Wild-type PICK1 rescues this phenotype, but a mutant PICK1, PICK1(W413A), that does not bind or inhibit Arp2/3 has no effect. Furthermore, this mutant also blocks NMDA-induced AMPAR internalization. This study identifies PICK1 as a negative regulator of Arp2/3-mediated actin polymerization that is critical for a specific form of vesicle trafficking, and also for the development of neuronal architecture.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据