Enhanced clathrin-dependent endocytosis in the absence of calnexin

PLoS One. 2011;6(7):e21678. doi: 10.1371/journal.pone.0021678. Epub 2011 Jul 1.

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.

Methodology/principal findings: 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/significance: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calnexin / chemistry
  • Calnexin / deficiency*
  • Calnexin / metabolism
  • Clathrin / metabolism*
  • Cytoplasm / metabolism
  • Endocytosis*
  • Ligands
  • Mice

Substances

  • Clathrin
  • Ligands
  • Calnexin