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

Dev Cell. 2021 Mar 22;56(6):842-859.e8. doi: 10.1016/j.devcel.2021.02.029.


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.

Keywords: I-BAR; MIM; exosome; filopodia; filopodia-derived vesicle (FDV); large extracellular vesicle (l-EV); microvesicle; small extracellular vesicle (s-EV).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Membrane / metabolism
  • Cell Movement*
  • Endocytosis*
  • Endosomal Sorting Complexes Required for Transport / genetics
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Exosomes / metabolism*
  • Extracellular Vesicles / metabolism*
  • HEK293 Cells
  • Humans
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Pseudopodia / metabolism*


  • Calcium-Binding Proteins
  • Cell Cycle Proteins
  • Endosomal Sorting Complexes Required for Transport
  • MTSS1 protein, human
  • Microfilament Proteins
  • Neoplasm Proteins
  • PDCD6IP protein, human