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血小板中，Scar/WAVE-1在糖蛋白VI下游发挥主要作用。

A major role for Scar/WAVE-1 downstream of GPVI in platelets.

作者信息

Calaminus S D J, McCarty O J T, Auger J M, Pearce A C, Insall R H, Watson S P, Machesky L M

机构信息

Centre for Cardiovascular Sciences, Institute of Biomedical Research, The Medical School, University of Birmingham, Birmingham, UK.

出版信息

J Thromb Haemost. 2007 Mar;5(3):535-41. doi: 10.1111/j.1538-7836.2007.02377.x.

DOI:10.1111/j.1538-7836.2007.02377.x
PMID:17319906
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1880834/
Abstract

BACKGROUND

The small GTPase Rac1 plays a critical role in lamellipodia assembly in platelets on matrix proteins in the absence or presence of G protein-coupled receptor (GPCR) agonists. Rac mediates actin assembly via Scar/WAVE, a family of scaffolding proteins that direct actin reorganization by relaying signals from Rac to the Arp2/3 complex.

OBJECTIVE

To evaluate the role of Scar/WAVE-1 in mediating platelet activation and cytoskeletal reorganization.

METHODS AND RESULTS

Using specific antibodies, we demonstrate that murine platelets, like human platelets, express Scar/WAVE-1 and Scar/WAVE-2. Lamellipodia formation in Scar/WAVE-1(-/-) platelets is markedly inhibited on immobilized collagen-related peptide (CRP) and on laminin, both of which signal through the collagen receptor GPVI. In contrast, lamellipodia formation on collagen, which requires release of the GPCR agonists ADP and thromboxane A(2), is not altered. Immobilized fibrinogen supports limited formation of lamellipodia in murine platelets, which is not altered in Scar/WAVE-1(-/-) platelets. As with Rac1(-/-) platelets, Scar/WAVE-1(-/-) platelets exhibit a marked inhibition of aggregation in response to CRP, whereas the response to the GPCR agonist thrombin is not altered. Platelet aggregation on immobilized collagen under shear, which is dependent on signaling by matrix and GPCR agonists, was unaltered in the absence of Scar/WAVE-1.

CONCLUSION

This study demonstrates a major role for Scar/WAVE-1 in mediating platelet cytoskeletal reorganization and aggregate formation downstream of activation by GPVI but not by GPCR agonists.

摘要

背景

小GTP酶Rac1在血小板在基质蛋白上形成片状伪足的过程中起着关键作用，无论是否存在G蛋白偶联受体（GPCR）激动剂。Rac通过Scar/WAVE介导肌动蛋白组装，Scar/WAVE是一类支架蛋白家族，通过将信号从Rac传递到Arp2/3复合物来指导肌动蛋白重组。

目的

评估Scar/WAVE-1在介导血小板活化和细胞骨架重组中的作用。

方法与结果

使用特异性抗体，我们证明小鼠血小板与人血小板一样，表达Scar/WAVE-1和Scar/WAVE-2。在固定化胶原相关肽（CRP）和层粘连蛋白上，Scar/WAVE-1基因敲除（-/-）血小板的片状伪足形成受到显著抑制，这两种物质均通过胶原受体GPVI发出信号。相比之下，在需要释放GPCR激动剂ADP和血栓素A2的胶原上的片状伪足形成没有改变。固定化纤维蛋白原支持小鼠血小板中有限的片状伪足形成，在Scar/WAVE-1（-/-）血小板中这一情况没有改变。与Rac1（-/-）血小板一样，Scar/WAVE-1（-/-）血小板对CRP的聚集反应受到显著抑制，而对GPCR激动剂凝血酶的反应没有改变。在剪切力作用下，固定化胶原上的血小板聚集依赖于基质和GPCR激动剂的信号传导，在没有Scar/WAVE-1的情况下未发生改变。

结论

本研究证明Scar/WAVE-1在介导血小板细胞骨架重组以及GPVI而非GPCR激动剂激活下游的聚集形成中起主要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbda/1880834/5e5008078ff4/nihms-544-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbda/1880834/645392da9bee/nihms-544-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbda/1880834/aee77f6b15ce/nihms-544-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbda/1880834/bba9f30a65d2/nihms-544-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbda/1880834/3839989d99b9/nihms-544-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbda/1880834/602d0006314c/nihms-544-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbda/1880834/5e5008078ff4/nihms-544-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbda/1880834/645392da9bee/nihms-544-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbda/1880834/aee77f6b15ce/nihms-544-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbda/1880834/bba9f30a65d2/nihms-544-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbda/1880834/3839989d99b9/nihms-544-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbda/1880834/602d0006314c/nihms-544-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbda/1880834/5e5008078ff4/nihms-544-f0006.jpg

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