SCAR knockouts in Dictyostelium: WASP assumes SCAR's position and upstream regulators in pseudopods.
SCAR knockouts in Dictyostelium: WASP assumes SCAR's position and upstream regulators in pseudopods.
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DOI：
10.1083/jcb.201205058
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发表时间：
2012-08-20
期刊：
影响因子：
--
通讯作者：
Insall RH
中科院分区：
文献类型：
--
作者：
Veltman DM;King JS;Machesky LM;Insall RH
在没有SCAR的情况下，网柄藻WASP从被膜凹坑重新定位到细胞的前缘，并被激活以驱动伪足形成。在正常条件下，Arp 2/3复合物激活剂SCAR/WAVE控制伪足中的肌动蛋白聚合，而Wiskott-Aldrich综合征蛋白（WASP）在网格蛋白包被的凹陷处组装肌动蛋白。我们发现，出乎意料的是，Dictyosteelium discoideum SCAR敲除仍然可以使用Arp 2/3复合物驱动的伪足传播，迁移和chemotax。在没有SCAR的情况下，一些WASP从涂层凹坑重新定位到前缘，在那里它表现出与正常SCAR相似的动力学，形成分裂的伪足和行波。无论是由WASP还是SCAR驱动，伪足与活性Rac共定位，尽管在SCAR突变体中Rac被激活到更高的水平。SCAR监管复合体的成员，特别是PIR 121，不需要WASP监管。因此，我们表明，WASP是能够响应所有的核心上游信号和监管机构耦合通过SCAR的监管复合物的其他成员是不是必不可少的伪足形成。我们的结论是，WASP和SCAR可以调节伪足肌动蛋白使用类似的机制。
In the absence of SCAR, Dictyostelium WASP is relocalized from coated pits to the leading edge of the cell and activated to drive pseudopod formation. Under normal conditions, the Arp2/3 complex activator SCAR/WAVE controls actin polymerization in pseudopods, whereas Wiskott–Aldrich syndrome protein (WASP) assembles actin at clathrin-coated pits. We show that, unexpectedly, Dictyostelium discoideum SCAR knockouts could still spread, migrate, and chemotax using pseudopods driven by the Arp2/3 complex. In the absence of SCAR, some WASP relocated from the coated pits to the leading edge, where it behaved with similar dynamics to normal SCAR, forming split pseudopods and traveling waves. Pseudopods colocalized with active Rac, whether driven by WASP or SCAR, though Rac was activated to a higher level in SCAR mutants. Members of the SCAR regulatory complex, in particular PIR121, were not required for WASP regulation. We thus show that WASP is able to respond to all core upstream signals and that regulators coupled through the other members of SCAR’s regulatory complex are not essential for pseudopod formation. We conclude that WASP and SCAR can regulate pseudopod actin using similar mechanisms.
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DOI：
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发表时间：
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期刊：
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影响因子：
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通讯作者：
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