Monoubiquitination of EEA1 regulates endosome fusion and trafficking

BackgroundEarly endosomal autoantigen 1 (EEA1) is a membrane tethering factor required for the fusion and maturation of early endosomes in endocytosis. How the activity of EEA1 is regulated in cells is unclear.ResultsHere we show that endogenous EEA1 is prone to monoubiquitination at multiple sites, owing to an intrinsic affinity to ubiquitin conjugating enzymes (E2). The E2 interactions enable a ubiquitin ligase (E3) independent mechanism that decorate EEA1 with multiple mono-ubiquitin moieties. Expression of an ubiquitin-EEA1 chimera that mimics native mono-ubiquitinated EEA1 generates giant endosomes abutting the nucleus. Several lines of evidence suggest that this phenotype is due to increased endosome fusion and a simultaneous blockade on an endosome recycling pathway. The latter is likely caused by diminished endosome fission in cells expressing ubiquitin-EEA1.ConclusionOur results demonstrate that ubiquitination may dramatically affect the activity of an endosome fusion factor to alter endosome morphology and trafficking pattern, and thereby implicating an unexpected role of ubiquitin signaling in endocytosis.

• Publication year

  2013

• Venue

  Cell & Bioscience

• Publication date

  2013-05-23

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/2045-3701-3-24PMID 23701900PMCID 3673817
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2012cited by this paper
• The p97 ATPase associates with EEA1 to regulate the size of early endosomes

  2011cited by this paper
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  2011cited by this paper
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  2011cited by this paper
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  2010cited by this paper
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  2010cited by this paper
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  2010cited by this paper
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  2009cited by this paper
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  2009cited by this paper
• Building ubiquitin chains: E2 enzymes at work

  2009cited by this paper
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  2008cited by this paper
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  2007cited by this paper
• Cdc48/p97 promotes reformation of the nucleus by extracting the kinase Aurora B from chromatin

  2007cited by this paper
• E3-independent monoubiquitination of ubiquitin-binding proteins.

  2007cited by this paper
• Endocytosis: the DUB version.

  2006cited by this paper
• Diverse functions with a common regulator: ubiquitin takes command of an AAA ATPase.

  2006cited by this paper
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  2005cited by this paper
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  2004cited by this paper
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  2003cited by this paper
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  2003cited by this paper
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  2001cited by this paper
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  2001cited by this paper
• Oligomeric complexes link Rab5 effectors with NSF and drive membrane fusion via interactions between EEA1 and syntaxin 13.

  1999cited by this paper
• Regulation of endosome fusion.

  1999cited by this paper
• FYVE finger proteins as effectors of phosphatidylinositol 3-phosphate.

  1999cited by this paper
• The Rab5 effector EEA1 is a core component of endosome docking

  1999cited by this paper
• Phosphatidylinositol 3-phosphate recognition by the FYVE domain.

  1999cited by this paper
• EEA1 links PI(3)K function to Rab5 regulation of endosome fusion

  1998cited by this paper
• Endosomal Localization of the Autoantigen EEA1 Is Mediated by a Zinc-binding FYVE Finger*

  1996cited by this paper
• Inhibition of rab5 GTPase activity stimulates membrane fusion in endocytosis.

  1994cited by this paper

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