CIN85 associates with endosomal membrane and binds phosphatidic acid.
CIN85 (Cbl-interacting protein of 85 kDa) is an important molecule involved in receptor tyrosine kinase endocytosis. Here we report that through its positively charged C-terminus, CIN85 associates with a fusogenic lipid - phosphatidic acid. Its coiled-coil domain plays an important role in mediating this protein-lipid interaction. Deletion of the coiled-coil ... domain results in loss of membrane association, and reduced interaction with c-cbl, finally causing the blockage of epidermal growth factor receptor downregulation. In addition, a significant portion of CIN85 is located on the endosomal compartment and is related to endocytic cargo sorting, characterized by CIN85's localization on the "E class" compartment and EGF degradation blockage in CIN85 knockdown cells. Taken together, our results suggest that CIN85 may function as a scaffold molecule in both the internalization and endocytic cargo sorting processes through its association with the endosomal membrane.
Mesh Terms:
Animals, COS Cells, Cell Line, Cell Membrane, Cercopithecus aethiops, Down-Regulation, Endocytosis, Endosomes, Gene Knockdown Techniques, Humans, Mice, Neoplasm Proteins, Nerve Tissue Proteins, Phosphatidic Acids, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins c-cbl, Receptor, Epidermal Growth Factor
Animals, COS Cells, Cell Line, Cell Membrane, Cercopithecus aethiops, Down-Regulation, Endocytosis, Endosomes, Gene Knockdown Techniques, Humans, Mice, Neoplasm Proteins, Nerve Tissue Proteins, Phosphatidic Acids, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins c-cbl, Receptor, Epidermal Growth Factor
Cell Res.
Date: Jun. 01, 2009
PubMed ID: 19417776
View in: Pubmed Google Scholar
Download Curated Data For This Publication
134354
Switch View:
- Interactions 2