ORIGINAL ARTICLE

Cell Research (2009): 733-746
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CIN85 associates with endosomal membrane and binds phosphatidic acid

Jing Zhang, Xiudan Zheng, Xiao Yang and Kan Liao

Correspondence: Kan Liao, Tel: +86-21-54921113; Fax: +86-21-54921011 E-mail: kliao@sibs.ac.cn

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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.

Cell Research (2009) 19:733–746. doi: 10.1038/cr.2009.51; published online 5 May 2009

Keywords: CIN85, the coiled-coil domain, phosphatidic acid, EGFR endocytosis, ESCRT assembly