FCHSD2 cooperates with CDC42 and N-WASP to regulate cell protrusion formation
FCHSD2 cooperates with CDC42 and N-WASP to regulate cell protrusion formation
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FCHSD2与CDC42和N-WASP合作调节细胞突起形成
DOI：
10.1016/j.bbamcr.2021.119134
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Xu Zhigang
中科院分区：
文献类型：
--
作者：
Zhai Xiaoyan;Shen Yuxin;Zhang Xiujuan;Li Tianhao;Lu Qing;Xu Zhigang
以肌动蛋白为基础的指状细胞突起如微绒毛和丝状伪足在上皮细胞中起重要作用。已经鉴定出几种蛋白质来调节细胞突起的形成，这有助于我们了解这一过程的潜在机制。含FCH结构域和双SH 3结构域的蛋白2（FCHSD 2）属于FCH和Bin-两性霉素-Rvs（F-BAR）蛋白家族，含有N-末端F-BAR结构域、两个SH 3结构域和C-末端PDZ结构域结合界面（PBI）。以前，我们发现FCHSD 2与WASP/N-WASP相互作用，并在体外刺激ARP 2/3介导的肌动蛋白聚合。在目前的工作中，我们表明，FCHSD 2促进培养细胞的顶端和侧面细胞突起的形成。我们的数据表明，FCHSD 2协同CDC 42和N-WASP调节顶端细胞突起的形成。与此一致，生物化学研究表明FCHSD 2和CDC 42同时结合N-WASP，形成蛋白质复合物。有趣的是，FCHSD 2的F-BAR结构域独立于N-WASP诱导侧向细胞突起形成。此外，我们发现FCHSD 2诱导细胞突起形成的能力需要其质膜结合能力。总之，我们目前的工作表明，FCHSD 2与CDC 42和N-WASP合作，以膜依赖的方式调节细胞突起的形成。
Actin-based, finger-like cell protrusions such as microvilli and filopodia play important roles in epithelial cells. Several proteins have been identified to regulate cell protrusion formation, which helps us to learn about the underlying mechanism of this process. FCH domain and double SH3 domains containing protein 2 (FCHSD2) belongs to the FCH and Bin-Amphiphysin-Rvs (F-BAR) protein family, containing an N-terminal F-BAR domain, two SH3 domains, and a C-terminal PDZ domain-binding interface (PBI). Previously, we found that FCHSD2 interacts with WASP/N-WASP and stimulates ARP2/3-mediated actin polymerization in vitro. In the present work, we show that FCHSD2 promotes the formation of apical and lateral cell protrusions in cultured cells. Our data suggest that FCHSD2 cooperates with CDC42 and N-WASP in regulating apical cell protrusion formation. In line with this, biochemical studies reveal that FCHSD2 and CDC42 simultaneously bind to N-WASP, forming a protein complex. Interestingly, the F-BAR domain of FCHSD2 induces lateral cell protrusion formation independently of N-WASP. Furthermore, we show that the ability of FCHSD2 to induce cell protrusion formation requires its plasma membrane-binding ability. In summary, our present work suggests that FCHSD2 cooperates with CDC42 and N-WASP to regulate cell protrusion formation in a membrane-dependent manner.