The lipid-binding D4 domain of perfringolysin O facilitates the active loading of exogenous cargo into extracellular vesicles

被引：0

作者：

Opadele, Abayomi Emmanuel ^{[1
]}

Nishioka, Soichiro ^{[2
]}

Wu, Ping-Hsiu ^{[3
]}

Le, Quynh-Thu ^{[4
]}

Shirato, Hiroki ^{[2
]}

Nam, Jin-Min ^{[2
,5
]}

Onodera, Yasuhito ^{[2
]}

机构：

[1] Hokkaido Univ, Grad Sch Biomed Sci & Engn, Lab Mol & Cellular Dynam Res, Sapporo, Hokkaido, Japan

[2] Hokkaido Univ, Fac Med, Global Ctr Biomed Sci & Engn GCB, Sapporo, Hokkaido, Japan

[3] Taipei Med Univ, Coll Med, Sch Med, Dept Radiol, Taipei, Taiwan

[4] Stanford Univ, Dept Radiat Oncol, Sch Med, Stanford, CA USA

[5] Kyoto Univ, Grad Sch Biostudies, Div Syst Life Sci, Kyoto, Japan

来源：

FEBS LETTERS | 2024年 / 598卷 / 04期

关键词：

domain; 4; extracellular vesicles; protein delivery; split luciferase; CHOLESTEROL; TETRASPANIN; EXOSOMES; CD9; DELIVERY; PROTEINS;

D O I：

10.1002/1873-3468.14807

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Whereas extracellular vesicles (EVs) have been engineered for cargo loading, innovative strategies for it can still be developed. Here, we describe domain 4 (D4), a cholesterol-binding domain derived from perfringolysin O, as a viable candidate for EV cargo loading. D4 and its mutants localized to the plasma membrane and the membranes of different vesicular structures in the cytoplasm, and facilitate the transport of proteins of interest (POIs) into EVs. D4-EVs were internalized by recipient cells analogous to EVs engineered with CD9. Intracellular cargo discharge from D4-EVs was successfully detected with the assistance of vesicular stomatitis virus glycoprotein. This study presents a novel strategy for recruiting POIs into EVs via a lipid-binding domain that ensures content release in recipient cells.

引用

页码：446 / 456

页数：11

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