The WD40 and FYVE domain containing protein 2 defines a class of early endosomes necessary for endocytosis
Authors
Hayakawa, AkiraLeonard, Deborah Marie
Murphy, Stephanie
Hayes, Susan J.
Soto, Martha C.
Fogarty, Kevin E.
Standley, Clive
Bellve, Karl D.
Lambright, David G.
Mello, Craig C.
Corvera, Silvia
UMass Chan Affiliations
Department of PhysiologyProgram in Molecular Medicine and Biomedical Imaging Group
Document Type
Journal ArticlePublication Date
2006-07-29Keywords
Amino Acid Sequence; Animals; COS Cells; Caenorhabditis elegans; Cell Membrane; Cercopithecus aethiops; *Endocytosis; Endosomes; Green Fluorescent Proteins; Hela Cells; Humans; Intracellular Signaling Peptides and Proteins; Molecular Sequence Data; Phosphatidylinositol Phosphates; Protein Structure, TertiaryLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
The FYVE domain binds with high specificity and avidity to phosphatidylinositol 3-phosphate. It is present in approximately 30 proteins in humans, some of which have been implicated in functions ranging from early endosome fusion to signal transduction through the TGF-beta receptor. To develop a further understanding of the biological roles of this protein family, we turned to the nematode Caenorhabditis elegans, which contains only 12 genes predicted to encode for phosphatidylinositol 3-phosphate binding, FYVE domain-containing proteins, all of which have homologs in the human genome. Each of these proteins was targeted individually by RNA interference. One protein, WDFY2, produced a strong inhibition of endocytosis when silenced. WDFY2 contains WD40 motifs and a FYVE domain, is highly conserved between species, and localizes to a set of small endosomes that reside within 100 nm from the plasma membrane. These endosomes are involved in transferrin uptake but lack the classical endosomal markers Rab5 and EEA1. Silencing of WDFY2 by siRNA in mammalian cells impaired transferrin endocytosis. These studies reveal the important, conserved role of WDFY2 in endocytosis, and the existence of a subset of early endosomes, closely associated with the plasma membrane, that may constitute the first stage of endocytic processing of internalized cargo.Source
Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11928-33. Epub 2006 Jul 27. Link to article on publisher's siteDOI
10.1073/pnas.0508832103Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33824PubMed ID
16873553Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1073/pnas.0508832103