UBL3 modification influences protein sorting to small extracellular vesicles

被引：66

作者：

Ageta, Hiroshi ^{[1
,2
]}

Ageta-Ishihara, Natsumi ^{[3
]}

Hitachi, Keisuke ^{[1
]}

Karayel, Ozge ^{[4
]}

Onouchi, Takanori ^{[5
]}

Yamaguchi, Hisateru ^{[6
]}

Kahyo, Tomoaki ^{[2
,7
]}

Hatanaka, Ken ^{[2
,17
]}

Ikegami, Koji ^{[2
,8
,9
,19
,20
]}

Yoshioka, Yusuke ^{[10
,11
]}

Nakamura, Kenji ^{[2
,18
]}

Kosaka, Nobuyoshi ^{[10
,11
]}

Nakatani, Masashi ^{[1
]}

Uezumi, Akiyoshi ^{[1
]}

Ide, Tomihiko ^{[12
]}

Tsutsumi, Yutaka ^{[5
]}

Sugimura, Haruhiko ^{[7
]}

Kinoshita, Makoto ^{[3
]}

Ochiya, Takahiro ^{[10
,13
]}

Mann, Matthias ^{[4
]}

Setou, Mitsutoshi ^{[2
,8
,9
,14
,15
,16
]}

Tsuchida, Kunihiro ^{[1
]}

机构：

[1] Fujita Hlth Univ, Inst Comprehens Med Sci, Div Therapies Intractable Dis, 1-98 Dengakugakubo,Kutsukake Cho, Toyoake, Aichi 4701192, Japan

[2] Mitsubishi Kagaku Inst Life Sci MITILS, 11 Minamiooya, Tokyo 1948511, Japan

[3] Nagoya Univ, Grad Sch Sci, Dept Mol Biol, Div Biol Sci, Nagoya, Aichi 4648602, Japan

[4] Max Planck Inst Biochem, Dept Prote & Signal Transduct, D-82152 Martinsried, Germany

[5] Fujita Hlth Univ, Sch Med, Dept Pathol, 1-98 Dengakugakubo,Kutsukake Cho, Toyoake, Aichi 4701192, Japan

[6] Fujita Hlth Univ, Inst Comprehens Med Sci, Div Biomed Polymer Sci, 1-98 Dengakugakubo,Kutsukake Cho, Toyoake, Aichi 4701192, Japan

[7] Hamamatsu Univ Sch Med, Dept Tumor Pathol, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan

[8] Hamamatsu Univ Sch Med, Dept Cellular & Mol Anat, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan

[9] Hamamatsu Univ Sch Med, Int Mass Imaging Ctr, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan

[10] Natl Canc Ctr, Res Inst, Div Mol & Cellular Med, Chuo Ku, 5-1-1 Tsukiji, Tokyo 1040045, Japan

[11] Tokyo Med Univ, Dept Translat Res Extracellular Vesicles, Shinjuku Ku, 6-7-1 Nishi Shinjuku, Tokyo 1600023, Japan

[12] Fujita Hlth Univ, Joint Res Support Promot Facil, Lab Elect Microscopy, 1-98 Dengakugakubo,Kutsukake Cho, Toyoake, Aichi 4701192, Japan

[13] Tokyo Med Univ, Inst Med Sci, Shinjuku Ku, 6-7-1 Nishi Shinjuku, Tokyo 1600023, Japan

[14] Preeminent Med Photon Educ & Res Ctr, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan

[15] Univ Hong Kong, Dept Anat, 6-F,William MW Mong Block 21 Sassoon Rd, Pokfulam, Hong Kong, Peoples R China

[16] Fujita Hlth Univ, Sch Med, Dept Anat & Cell Biol & Anat 2, 1-98 Dengakugakubo,Kutsukake Cho, Toyoake, Aichi 4701192, Japan

[17] Eisai & Co Ltd, Neurol Business Grp, Neurol Tsukuba Res Dept Discovery Med Creat, 1-3 Tokodai 5-Chome, Tsukuba, Ibaraki 3002635, Japan

[18] Nitobebunka Coll, Dept Clin Lab Sci, Nakano Ku, 43-16 Nakano 3-Chome, Tokyo 1640001, Japan

[19] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Anat & Dev Biol, Minami Ku, 1-2-3 Kasumi, Hiroshima, Hiroshima 7348553, Japan

[20] JST, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 3320012, Japan

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

PROGENITOR CELLS; UBIQUITIN; EXOSOMES; IDENTIFICATION; MICROVESICLES; ASSOCIATION; PRIONS;

D O I：

10.1038/s41467-018-06197-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Exosomes, a type of small extracellular vesicles (sEVs), derived from multivesicular bodies (MVBs), mediate cell-to-cell communication by transporting proteins, mRNAs, and miRNAs. However, the molecular mechanism by which proteins are sorted to sEVs is not fully understood. Here, we report that ubiquitin-like 3 (UBL3)/membrane-anchored Ub-fold protein (MUB) acts as a posttranslational modification (PTM) factor that regulates protein sorting to sEVs. We find that UBL3 modification is indispensable for sorting of UBL3 to MVBs and sEVs. We also observe a 60% reduction of total protein levels in sEVs purified from Ubl3-knockout mice compared with those from wild-type mice. By performing proteomics analysis, we find 1241 UBL3-interacting proteins, including Ras. We also show that UBL3 directly modifies Ras and oncogenic RasG12V mutant, and that UBL3 expression enhances sorting of RasG12V to sEVs via UBL3 modification. Collectively, these results indicate that PTM by UBL3 influences the sorting of proteins to sEVs.

引用

页数：12

共 37 条

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