WASP family proteins, more than Arp2/3 activators.
WASP family proteins, more than Arp2/3 activators.
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DOI：
10.1042/bst20160176
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发表时间：
2016-10-15
影响因子：
3.9
通讯作者：
Ayscough KR
中科院分区：
文献类型：
--
作者：
Tyler JJ;Allwood EG;Ayscough KR
威斯科特 - 奥尔德里奇综合征蛋白（WASP）家族蛋白已被广泛认定为通过激活蛋白复合物Arp2/3来促进肌动蛋白成核的因子。酵母大多只有该家族的一个成员，而哺乳动物细胞至少有六个不同成员，且常常具有多种异构体。该家族成员具有共同的结构特征。它们的N末端各不相同，并被认为可对Arp2/3激活活性进行时空调节，而其C末端一半包含一个富含多聚脯氨酸的区域、一个或多个WASP同源结构域 - 2（WH2）肌动蛋白结合结构域以及直接与Arp2/3结合的基序。然而，近期研究表明，酵母WASP同系物Las17能够通过其多聚脯氨酸区域内新的G - 肌动蛋白结合活性，在不依赖Arp2/3的情况下使肌动蛋白成核。这使得Las17能够产生在酵母中驱动内吞内陷的肌动蛋白聚合过程中后续招募和激活Arp2/3所需的母丝。在这篇综述中，我们探讨Las17多聚脯氨酸区域内的基序如何支持肌动蛋白丝的成核，以及其他家族成员中是否可能存在类似机制。
Wiskott–Aldrich syndrome protein (WASP) family proteins have been extensively characterized as factors that promote the nucleation of actin through the activation of the protein complex Arp2/3. While yeast mostly have a single member of the family, mammalian cells have at least six different members, often with multiple isoforms. Members of the family are characterized by a common structure. Their N-termini are varied and are considered to confer spatial and temporal regulation of Arp2/3-activating activity, whereas their C-terminal half contains a polyproline-rich region, one or more WASP homology-2 (WH2) actin-binding domains and motifs that bind directly to Arp2/3. Recent studies, however, indicate that the yeast WASP homologue Las17 is able to nucleate actin independently of Arp2/3 through the function of novel G-actin-binding activities in its polyproline region. This allows Las17 to generate the mother filaments that are needed for subsequent Arp2/3 recruitment and activation during the actin polymerization that drives endocytic invagination in yeast. In this review, we consider how motifs within the polyproline region of Las17 support nucleation of actin filaments, and whether similar mechanisms might exist among other family members.