TY - JOUR
T1 - Filopodium-derived vesicles produced by MIM enhance the migration of recipient cells
AU - Nishimura, Tamako
AU - Oyama, Takuya
AU - Hu, Hooi Ting
AU - Fujioka, Toshifumi
AU - Hanawa-Suetsugu, Kyoko
AU - Ikeda, Kazutaka
AU - Yamada, Sohei
AU - Kawana, Hiroki
AU - Saigusa, Daisuke
AU - Ikeda, Hiroki
AU - Kurata, Rie
AU - Oono-Yakura, Kayoko
AU - Kitamata, Manabu
AU - Kida, Kazuki
AU - Hikita, Tomoya
AU - Mizutani, Kiyohito
AU - Yasuhara, Kazuma
AU - Mimori-Kiyosue, Yuko
AU - Oneyama, Chitose
AU - Kurimoto, Kazuki
AU - Hosokawa, Yoichiroh
AU - Aoki, Junken
AU - Takai, Yoshimi
AU - Arita, Makoto
AU - Suetsugu, Shiro
N1 - Funding Information:
We thank our laboratory members for their technical assistance and helpful discussions. This work was supported by grants from JSPS (KAKENHI 26291037 , 15H01641 , 15H05897 , 15H05902 , 17H03674 , 17H06006 , 20H03252 ), from JST (CREST JPMJCR1863 ), the Uehara Memorial Foundation , the Osaka Cancer Research Foundation , the Naito Foundation , the Sumitomo Foundation , the Mitsubishi Foundation , the Sagawa Foundation for Promotion of Cancer Research , the Sumitomo Foundation, the Grant for Joint Research Project of the Institute of Medical Sciences, The University of Tokyo , the Extramural Collaborative Research Grant of Cancer Research Institute at Kanazawa University , and the NAIST Interdisciplinary Frontier Research Project and the Data Science Center to S.S.; the NEXT program ( LS128 ), Takeda Science Foundation , the Uehara Memorial Foundation, JSPS (KAKENHI 20K20379 ), and JST (CREST JPMJCR1863 ) to Y. M.-K.; JSPS (KAKENHI 17K07427 , 20K06625 ) to T.N., and JSPS (KAKENHI 16K07351 , 19K06639 ) to K.H.-S.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/3/22
Y1 - 2021/3/22
N2 - 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.
AB - 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.
KW - I-BAR
KW - MIM
KW - exosome
KW - filopodia
KW - filopodia-derived vesicle (FDV)
KW - large extracellular vesicle (l-EV)
KW - microvesicle
KW - small extracellular vesicle (s-EV)
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UR - http://www.scopus.com/inward/citedby.url?scp=85102626038&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2021.02.029
DO - 10.1016/j.devcel.2021.02.029
M3 - Article
C2 - 33756122
AN - SCOPUS:85102626038
SN - 1534-5807
VL - 56
SP - 842-859.e8
JO - Developmental Cell
JF - Developmental Cell
IS - 6
ER -