Biology:EEA1
 Generic protein structure example |
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.[1][2]
EEA1 plays a role in endocytosis and is recruited by Rab5-GTP to endosomal membranes.[3] EEA1 may be regulated through monoubiquination, affecting endosome fusion and trafficking.[4] Ubiquitin selective segregase p97 may regulate EEA1's tethering ability, affecting its endosome trafficking and morphplogy.
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.[5] Legionella pneumophila also prevents EEA1 recruitment through a currently unknown mechanism.[6] The related pathogen Legionella longbeachae recruits EEA1 and appears to replicate within a modified early endosome.[7]
See also
References
- ↑ "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 107 (24): 10866–71. Jun 2010. doi:10.1073/pnas.1000843107. PMID 20534488. Bibcode: 2010PNAS..10710866M.
- ↑ "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 106 (24): 9697–702. Jun 2009. doi:10.1073/pnas.0901444106. PMID 19487677. PMC 2691687. Bibcode: 2009PNAS..106.9697B. http://pubman.mpdl.mpg.de/pubman/item/escidoc:588073/component/escidoc:2213586/588073.pdf.
- ↑ "Chapter 138 - FYVE Domains in Membrane Trafficking and Cell Signaling" (in en). Handbook of Cell Signaling (Second ed.). San Diego: Academic Press. January 2010. pp. 1111–1121. doi:10.1016/B978-0-12-374145-5.00138-8. ISBN 978-0-12-374145-5.
- ↑ "Monoubiquitination of EEA1 regulates endosome fusion and trafficking". Cell & Bioscience 3 (1): 24. May 2013. doi:10.1186/2045-3701-3-24. PMID 23701900.
- ↑ "Cutting edge: Mycobacterium tuberculosis blocks Ca2+ signaling and phagosome maturation in human macrophages via specific inhibition of sphingosine kinase". Journal of Immunology 170 (6): 2811–5. Mar 2003. doi:10.4049/jimmunol.170.6.2811. PMID 12626530.
- ↑ "Proteome analysis of Legionella vacuoles purified by magnetic immunoseparation reveals secretory and endosomal GTPases". Traffic 10 (1): 76–87. Jan 2009. doi:10.1111/j.1600-0854.2008.00851.x. PMID 18980612.
- ↑ "Early trafficking and intracellular replication of Legionella longbeachaea within an ER-derived late endosome-like phagosome". Cellular Microbiology 9 (6): 1571–87. Jun 2007. doi:10.1111/j.1462-5822.2007.00894.x. PMID 17309675.
External links
- early+endosome+antigen+1 at the US National Library of Medicine Medical Subject Headings (MeSH)
- Overview of all the structural information available in the PDB for UniProt: Q15075 (Early endosome antigen 1) at the PDBe-KB.
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