AMSH, an ESCRT-III Associated Enzyme, Deubiquitinates Cargo on MVB/Late Endosomes

Cell Structure and Function

Akitsugu Yamamoto²  Katsuhiko Kojima³  Kazu Kikuchi¹  Junichi Goto⁴  Nariyasu Mano⁴  Masanao Kyuuma¹  Toshikazu Takeshita³  Mariko Sato¹  Nobuyuki Tanaka¹  Yuriko Sugawara¹  Kazuo Sugamura¹ 

[1] Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine;Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology;Department of Microbiology and Immunology, Shinshu University School of Medicine;Tohoku University Graduate School of Pharmaceutical Sciences

关键词: deubiquitination;    endosome;    ESCRT-III;    MVB;    ubiquitin;   

DOI  :  10.1247/csf.06023

学科分类：分子生物学，细胞生物学和基因

来源: Japan Society for Cell Biology

【 摘 要 】

References(41)Cited-By(22)The appropriate sorting of vesicular cargo, including cell-surface proteins, is critical for many cellular functions. Ubiquitinated cargo is targeted to endosomes and digested by lysosomal enzymes. We previously identified AMSH, a deubiquitination enzyme (DUB), to be involved in vesicular transport. Here, we purified an AMSH-binding protein, CHMP3, which is an ESCRT-III subunit. ESCRT-III functions on maturing endosomes, indicating AMSH might also play a role in MVB/late endosomes. Expression of an AMSH mutant lacking CHMP3-binding ability resulted in aberrant endosomes with accumulations of ubiquitinated cargo. Nevertheless, CHMP3-binding capability was not essential for AMSH’s in vitro DUB activity or its endosomal localization, suggesting that, in vivo, the deubiquitination of endosomal cargo is CHMP3-dependent. Ubiquitinated cargo also accumulated on endosomes when catalytically inactive AMSH was expressed or AMSH was depleted. These results suggest that both the DUB activity of AMSH and its CHMP3-binding ability are required to clear ubiquitinated cargo from endosomes.

【 授权许可】

Unknown