Volume 19, No 6, Jun 2009

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 19 Issue 6, June 2009: 733-746

ORIGINAL ARTICLES

CIN85 associates with endosomal membrane and binds phosphatidic acid

Jing Zhang, Xiudan Zheng, Xiao Yang and Kan Liao

State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China Correspondence: Kan Liao,(kliao@sibs.ac.cn )

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

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