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EEA1

Protein-coding gene in humans

Protein-coding gene in humans

The gene EEA1 encodes for the 1400 amino acid protein, Early Endosome Antigen 1.

EEA1 localizes exclusively to early endosomes and has an important role in endosomal trafficking. EEA1 binds directly to the phospholipid phosphatidylinositol 3-phosphate through its C-terminal FYVE domain and forms a homodimer through a coiled coil. EEA1 acts as a tethering molecule that couples vesicle docking with SNAREs such as N-ethylmaleimide sensitive fusion protein, bringing the endosomes physically closer and ultimately resulting in the fusion and delivery of endosomal cargo.

Function

EEA1 is a RAB5A effector protein which binds via an N-terminal zinc finger domain and is required for fusion of early and late endosomes and for sorting at the early endosome level.

EEA1 plays a role in endocytosis and is recruited by Rab5-GTP to endosomal membranes. EEA1 may be regulated through monoubiquination, affecting endosome fusion and trafficking. Ubiquitin selective segregase p97 may regulate EEA1's tethering ability, affecting its endosome trafficking and morphology.

Involvement in pathogenesis

Due to the proteins importance in vesicular trafficking, a number of intracellular bacteria prevent EEA1 recruitment to the vacuole. Mycobacterium tuberculosis is known to inhibit the recruitment of EEA1 to the phagosomal membrane through CamKII. Legionella pneumophila also prevents EEA1 recruitment through a currently unknown mechanism. The related pathogen Legionella longbeachae recruits EEA1 and appears to replicate within a modified early endosome.

References

References

  1. (Jun 2010). "Structural basis for Rab GTPase recognition and endosome tethering by the C2H2 zinc finger of Early Endosomal Autoantigen 1 (EEA1)". Proceedings of the National Academy of Sciences of the United States of America.
  2. (Jun 2009). "Sorting in early endosomes reveals connections to docking- and fusion-associated factors". Proceedings of the National Academy of Sciences of the United States of America.
  3. (January 2010). "Handbook of Cell Signaling". Academic Press.
  4. (May 2013). "Monoubiquitination of EEA1 regulates endosome fusion and trafficking". Cell & Bioscience.
  5. (Mar 2003). "Cutting edge: Mycobacterium tuberculosis blocks Ca2+ signaling and phagosome maturation in human macrophages via specific inhibition of sphingosine kinase". Journal of Immunology.
  6. (Jan 2009). "Proteome analysis of Legionella vacuoles purified by magnetic immunoseparation reveals secretory and endosomal GTPases". Traffic.
  7. (Jun 2007). "Early trafficking and intracellular replication of Legionella longbeachaea within an ER-derived late endosome-like phagosome". Cellular Microbiology.
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