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.

基于肌动蛋白的指状细胞突起，如微绒毛和丝状伪足在上皮细胞中起重要作用。已经确定了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。FCH 域和双 SH3 域包含蛋白 2 (FCHSD2) 属于 FCH 和 Bin-Amphiphysin-Rvs (F-BAR) 蛋白家族，包含一个 N 端 F-BAR 域、两个 SH3 域和一个 C 端 PDZ域绑定接口 (PBI)。以前，我们发现 FCHSD2 与 WASP/N-WASP 相互作用并在体外刺激 ARP2/3 介导的肌动蛋白聚合。在目前的工作中，我们表明 FCHSD2 促进培养细胞中顶端和侧面细胞突起的形成。我们的数据表明 FCHSD2 与 CDC42 和 N-WASP 合作调节顶端细胞突起的形成。与此一致的是，生化研究表明 FCHSD2 和 CDC42 同时与 N-WASP 结合，形成蛋白质复合物。有趣的是，FCHSD2 的 F-BAR 结构域独立于 N-WASP 诱导横向细胞突起形成。此外，我们表明 FCHSD2 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 FCHSD2 与 CDC42 和 N-WASP 合作以膜依赖性方式调节细胞突起形成。我们表明 FCHSD2 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 FCHSD2 与 CDC42 和 N-WASP 合作以膜依赖性方式调节细胞突起形成。我们表明 FCHSD2 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 FCHSD2 与 CDC42 和 N-WASP 合作以膜依赖性方式调节细胞突起形成。