title: Enhanced clathrin-dependent endocytosis in the absence of calnexin.
abstract: BACKGROUND
  Calnexin, together with calreticulin, constitute the calnexin/calreticulin cycle. Calnexin is a type I endoplasmic reticulum integral membrane protein and molecular chaperone responsible for the folding and quality control of newly-synthesized (glyco)proteins. The endoplasmic reticulum luminal domain of calnexin is responsible for lectin-like activity and interaction with nascent polypeptide chains. The role of the C-terminal, cytoplasmic portion of calnexin is not clear.
  
  
  RESULTS
  Using yeast two hybrid screen and immunoprecipitation techniques, we showed that the Src homology 3-domain growth factor receptor-bound 2-like (Endophilin) interacting protein 1 (SGIP1), a neuronal specific regulator of endocytosis, forms complexes with the C-terminal cytoplasmic domain of calnexin. The calnexin cytoplasmic C-tail interacts with SGIP1 C-terminal domains containing the adaptor complexes medium subunit (Adap-Comp-Sub) region. Calnexin-deficient cells have enhanced clathrin-dependent endocytosis in neuronal cells and mouse neuronal system. This is reversed by expression of full length calnexin or calnexin C-tail.
  
  
  CONCLUSIONS
  We show that the effects of SGIP1 and calnexin C-tail on clathrin-dependent endocytosis are due to modulation of the internalization of the receptor-ligand complexes. Enhanced clathrin-dependent endocytosis in the absence of calnexin may contribute to the neurological phenotype of calnexin-deficient mice.
authors: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
authors: Hao-Dong
authors: HD
authors: Li
authors: Wen-Xin
authors: WX
authors: Liu
authors: Marek
authors: M
authors: Michalak
mesh_terms: D000818:Animals; D037281:Calnexin / Q000737:chemistry / Q000172:deficiency* / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004705:Endocytosis; D008024:Ligands; D051379:Mice
chemical_list: D002966:Clathrin; D008024:Ligands; D037281:Calnexin