GSBS Student Publications

Title

The WD40 and FYVE domain containing protein 2 defines a class of early endosomes necessary for endocytosis

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Program in Molecular Medicine and Biomedical Imaging Group; Department of Physiology

Date

7-29-2006

Document Type

Article

Medical Subject Headings

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, Tertiary

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11928-33. Epub 2006 Jul 27. Link to article on publisher's site

DOI of Published Version

10.1073/pnas.0508832103

Related Resources

Link to article in PubMed

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

16873553