The STRIPAK complex components FAM40A and FAM40B regulate endothelial cell contractility via ROCKs.

Q1 Biochemistry, Genetics and Molecular Biology

BMC Cell Biology Pub Date : 2018-12-03 DOI:10.1186/s12860-018-0175-y

Narendra Suryavanshi, Joanna Furmston, Anne J Ridley

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Abstract

Background: Endothelial cells provide a barrier between blood and tissues, which is regulated to allow molecules and cells in out of tissues. Patients with cerebral cavernous malformations (CCM) have dilated leaky blood vessels, especially in the central nervous system. A subset of these patients has loss-of-function mutations in CCM3. CCM3 is part of the STRIPAK protein complex that includes the little-characterized proteins FAM40A and FAM40B.

Results: We show here that FAM40A and FAM40B can interact with CCM3. Knockdown of CCM3, FAM40A or FAM40B in endothelial cells by RNAi causes an increase in stress fibers and a reduction in loop formation in an in vitro angiogenesis assay, which can be reverted by inhibiting the Rho-regulated ROCK kinases. FAM40B depletion also increases endothelial permeability.

Conclusions: These results demonstrate the importance of the FAM40 proteins for endothelial cell physiology, and suggest that they act as part of the CCM3-containing STRIPAK complex.

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STRIPAK 复合物成分 FAM40A 和 FAM40B 通过 ROCKs 调节内皮细胞的收缩性。

背景：内皮细胞是血液和组织之间的屏障，通过调节使分子和细胞进出组织。脑海绵畸形（CCM）患者的血管扩张渗漏，尤其是在中枢神经系统。这些患者中有一部分存在 CCM3 功能缺失突变。CCM3 是 STRIPAK 蛋白复合物的一部分，该复合物包括特征不明显的蛋白质 FAM40A 和 FAM40B：结果：我们在此发现，FAM40A和FAM40B能与CCM3相互作用。在体外血管生成试验中，通过 RNAi 方法敲除内皮细胞中的 CCM3、FAM40A 或 FAM40B 会导致应力纤维增加和环路形成减少，而抑制 Rho- 调节的 ROCK 激酶可以逆转这种情况。FAM40B 的耗竭也会增加内皮的通透性：这些结果证明了 FAM40 蛋白对内皮细胞生理的重要性，并表明它们是含 CCM3 的 STRIPAK 复合物的一部分。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMC Cell Biology 生物-细胞生物学

CiteScore

7.30

自引率

0.00%

发文量

审稿时长

12 months

期刊介绍： BMC Molecular and Cell Biology, formerly known as BMC Cell Biology, is an open access journal that considers articles on all aspects of both eukaryotic and prokaryotic cell and molecular biology, including structural and functional cell biology, DNA and RNA in a cellular context and biochemistry, as well as research using both the experimental and theoretical aspects of physics to study biological processes and investigations into the structure of biological macromolecules.