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

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....

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Published inCell Structure and Function Vol. 31; no. 2; pp. 159 - 172
Main Authors Kyuuma, Masanao, Kikuchi, Kazu, Kojima, Katsuhiko, Sugawara, Yuriko, Sato, Mariko, Mano, Nariyasu, Goto, Junichi, Takeshita, Toshikazu, Yamamoto, Akitsugu, Sugamura, Kazuo, Tanaka, Nobuyuki
Format Journal Article
LanguageEnglish
Published Japan Japan Society for Cell Biology 01.01.2006
Japan Science and Technology Agency
Subjects
Catalysis
Cell Line
deubiquitination
Endopeptidases - genetics
Endopeptidases - metabolism
Endosomal Sorting Complexes Required for Transport
endosome
Endosomes - metabolism
Endosomes - ultrastructure
ESCRT-III
Humans
Lysosomes - metabolism
Microscopy, Immunoelectron
MVB
Nerve Tissue Proteins - metabolism
Protein Binding
ubiquitin
Ubiquitin - metabolism
Ubiquitin Thiolesterase
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Summary: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.
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content type line 23
ISSN:0386-7196
1347-3700
DOI:10.1247/csf.06023