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.
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Jing
J
Zhang
Xiudan
X
Zheng
Xiao
X
Yang
Kan
K
Liao
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D002522:Chlorocebus aethiops; D015536:Down-Regulation; D004705:Endocytosis; D011992:Endosomes / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010712:Phosphatidic Acids; C498782:Sh3kbp1 protein, mouse; D050721:Proto-Oncogene Proteins c-cbl; D066246:ErbB Receptors