WH2 and proline-rich domains of WASP-family proteins collaborate to accelerate actin filament elongation.
WH2 and proline-rich domains of WASP-family proteins collaborate to accelerate actin filament elongation.
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DOI：
10.15252/embj.201797039
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发表时间：
2018-01-04
期刊：
影响因子：
--
通讯作者：
Mullins RD
中科院分区：
文献类型：
--
作者：
Bieling P;Hansen SD;Akin O;Li TD;Hayden CC;Fletcher DA;Mullins RD
已知WASP家族蛋白通过刺激Arp2/3复合物的丝成核活性来促进支链肌动蛋白网络的组装。在这里，我们发现WASP家族蛋白也可以作为聚合酶加速无帽肌动蛋白丝的延伸。当聚集在表面时，WASP家族蛋白可以驱动分支肌动蛋白网络生长得比直接结合可溶性单体快得多。这种聚合酶的活性源于两个调控序列的协同作用：(i)结合肌动蛋白的WASP同源2 （WH2）结构域，以及（ii）结合profile - actin复合物的富含脯氨酸的序列。在没有profilin的情况下，WH2结构域足以加速纤维伸长，但在profilin存在的情况下，需要富含脯氨酸的序列通过(i)将聚合能力强的肌动蛋白单体引入生长的丝端附近，以及（ii）促进肌动蛋白单体从profilin - actin复合物中穿梭到附近的WH2结构域来支持聚合酶活性。未被占用的WH2结构域短暂地与自由丝端结合，阻止它们的生长，并动态地将支链肌动蛋白网络连接到创建它的WASP家族蛋白上。因此，WH2和富含脯氨酸的序列之间的合作在细丝生长和系固之间取得了平衡。我们的工作将WASP家族蛋白在分支肌动蛋白网络组装中发挥的关键作用扩展到至少三个：(i)促进树突成核；（ii）将肌动蛋白网络连接到膜；（三）加速长丝伸长。
WASP‐family proteins are known to promote assembly of branched actin networks by stimulating the filament‐nucleating activity of the Arp2/3 complex. Here, we show that WASP‐family proteins also function as polymerases that accelerate elongation of uncapped actin filaments. When clustered on a surface, WASP‐family proteins can drive branched actin networks to grow much faster than they could by direct incorporation of soluble monomers. This polymerase activity arises from the coordinated action of two regulatory sequences: (i) a WASP homology 2 (WH2) domain that binds actin, and (ii) a proline‐rich sequence that binds profilin–actin complexes. In the absence of profilin, WH2 domains are sufficient to accelerate filament elongation, but in the presence of profilin, proline‐rich sequences are required to support polymerase activity by (i) bringing polymerization‐competent actin monomers in proximity to growing filament ends, and (ii) promoting shuttling of actin monomers from profilin–actin complexes onto nearby WH2 domains. Unoccupied WH2 domains transiently associate with free filament ends, preventing their growth and dynamically tethering the branched actin network to the WASP‐family proteins that create it. Collaboration between WH2 and proline‐rich sequences thus strikes a balance between filament growth and tethering. Our work expands the number of critical roles that WASP‐family proteins play in the assembly of branched actin networks to at least three: (i) promoting dendritic nucleation; (ii) linking actin networks to membranes; and (iii) accelerating filament elongation.
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DOI：
10.1038/nrm2867
发表时间：
2010-04
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
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肌动蛋白调节波复合物的结构和控制。
影响因子：
64.8
作者：
Chen, Zhucheng;Borek, Dominika;Padrick, Shae B.;Gomez, Timothy S.;Metlagel, Zoltan;Ismail, Ayman M.;Umetani, Junko;Billadeau, Daniel D.;Otwinowski, Zbyszek;Rosen, Michael K.
通讯作者：
Rosen, Michael K.
影响因子：
3.4
作者：
Dickinson, RB;Purich, DL
通讯作者：
Purich, DL
影响因子：
16
作者：
Bosch, Montserrat;Le, Kim Ho Diep;Carlier, Marie-France
通讯作者：
Carlier, Marie-France
DOI：
10.3109/10409230903277340
发表时间：
2009-11
影响因子：
6.5
作者：
Dominguez R
通讯作者：
Dominguez R