Filopodium-derived vesicles produced by MIM enhance the migration of recipient cells

Tamako Nishimura, Takuya Oyama, Hooi Ting Hu, Toshifumi Fujioka, Kyoko Hanawa-Suetsugu, Kazutaka Ikeda, Sohei Yamada, Hiroki Kawana, Daisuke Saigusa, Hiroki Ikeda, Rie Kurata, Kayoko Oono-Yakura, Manabu Kitamata, Kazuki Kida, Tomoya Hikita, Kiyohito Mizutani, Kazuma Yasuhara, Yuko Mimori-Kiyosue, Chitose Oneyama, Kazuki KurimotoYoichiroh Hosokawa, Junken Aoki, Yoshimi Takai, Makoto Arita, Shiro Suetsugu

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)842-859.e8
JournalDevelopmental Cell
Volume56
Issue number6
DOIs
Publication statusPublished - 2021 Mar 22

Keywords

  • I-BAR
  • MIM
  • exosome
  • filopodia
  • filopodia-derived vesicle (FDV)
  • large extracellular vesicle (l-EV)
  • microvesicle
  • small extracellular vesicle (s-EV)

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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