A di-leucine signal in the ubiquitin moiety: Possible involvement in ubiqutination-mediated endocytosis

Fubito Nakatsu, Machie Sakuma, Yo Matsuo, Hisashi Arase, Sho Yamasaki, Nobuhiro Nakamura, Takashi Saito, Hiroshi Ohno

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    72 Citations (Scopus)


    Some plasma membrane receptors in yeast are known to be internalized and degraded in lysosomes upon ligand-dependent ubiquitination. However, the role of ubiquitination in endocytosis and lysosomal degradation in higher eukaryotes has been controversial. In order to directly assess this question, we investigated the fate of chimeric molecules in which ubiquitin moiety was fused in-frame to the cytoplasmic region of membrane proteins. The chimeric proteins with the wild-type ubiquitin were endocytosed and delivered to lysosomes efficiently. Mutant ubiquitin with lysine-to-arginine substitution could still mediate endocytosis, suggesting that polyubiquitination is not required for the endocytosis. We next searched for the existence of an endocy-tosis signal(s) in the ubiquitin moiety, and identified a di-leucine signal, Leu43-Ile44. The Leu43-Ile44 sequence mediated endocytosis and lysosomal sorting in a Leu43-dependent manner. These results suggest that the di-leucine signal in ubiquitin can be involved in ubiquitination-mediated endocytosis and lysosomal targeting of membrane proteins.

    Original languageEnglish
    Pages (from-to)26213-26219
    Number of pages7
    JournalJournal of Biological Chemistry
    Issue number34
    Publication statusPublished - Aug 25 2000

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Molecular Biology
    • Cell Biology


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