Filopodium-derived vesicles produced by MIM enhance the migration of recipient cells
Filopodium-derived vesicles produced by MIM enhance the migration of recipient cells
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DOI：
10.1016/j.devcel.2021.02.029
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发表时间：
2021-03-22
影响因子：
11.8
通讯作者：
Suetsugu, Shiro
中科院分区：
文献类型：
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作者：
Nishimura, Tamako;Oyama, Takuya;Suetsugu, Shiro
细胞外囊泡（EV）被分类为大EV（I-EV，或微囊泡）和小EV（s-EV，或外来体）。S-EV被认为是通过主要依赖于ESCRT蛋白复合物的过程从内体产生的，包括ALG-2相互作用蛋白X（阿利克斯）。然而，从质膜产生l-EV的机制尚未确定。膜曲率是由bin-amphiphysin-rvs（BAR）家族蛋白产生的，其中逆BAR（I-BAR）蛋白参与丝状伪足突起。在这里，我们表明，I-BAR蛋白，包括在转移中缺失（MIM），通过切断丝状伪足产生I-EV。有趣的是，含MIM的I-EV生产通过体内等效外力和通过抑制阿利克斯来促进，这表明囊泡形成的替代机制是s-EV。MIM依赖性I-EV含有溶血磷脂和蛋白质，包括IRS 4和Rac 1，其通过板状伪足形成刺激受体细胞的迁移。因此，这些丝状伪足依赖性l-EV，我们称之为丝状伪足衍生囊泡（FDV），改变细胞行为。
Extracellular vesicles (EVs) are classified as large EVs (l-EVs, or microvesicles) and small EVs (s-EVs, or exosomes). S-EVs are thought to be generated from endosomes through a process that mainly depends on the ESCRT protein complex, including ALG-2 interacting protein X (ALIX). However, the mechanisms of l-EV generation from the plasma membrane have not been identified. Membrane curvatures are generated by the bin-amphiphysin-rvs (BAR) family proteins, among which the inverse BAR (I-BAR) proteins are involved in filopodial protrusions. Here, we show that the I-BAR proteins, including missing in metastasis (MIM), generate l-EVs by scission of filopodia. Interestingly, MIM-containing l-EV production was promoted by in vivo equivalent external forces and by the suppression of ALIX, suggesting an alternative mechanism of vesicle formation to s-EVs. The MIM-dependent l-EVs contained lysophospholipids and proteins, including IRS4 and Rac1, which stimulated the migration of recipient cells through lamellipodia formation. Thus, these filopodia-dependent l-EVs, which we named as filopodia-derived vesicles (FDVs), modify cellular behavior.