title: SUMOylation of EHD3 Modulates Tubulation of the Endocytic Recycling Compartment.
abstract: Endocytosis defines the entry of molecules or macromolecules through the plasma membrane as well as membrane trafficking in the cell. It depends on a large number of proteins that undergo protein-protein and protein-phospholipid interactions. EH Domain containing (EHDs) proteins formulate a family, whose members participate in different stages of endocytosis. Of the four mammalian EHDs (EHD1-EHD4) EHD1 and EHD3 control traffic to the endocytic recycling compartment (ERC) and from the ERC to the plasma membrane, while EHD2 modulates internalization. Recently, we have shown that EHD2 undergoes SUMOylation, which facilitates its exit from the nucleus, where it serves as a co-repressor. In the present study, we tested whether EHD3 undergoes SUMOylation and what is its role in endocytic recycling. We show, both in-vitro and in cell culture, that EHD3 undergoes SUMOylation. Localization of EHD3 to the tubular structures of the ERC depends on its SUMOylation on lysines 315 and 511. Absence of SUMOylation of EHD3 has no effect on its dimerization, an important factor in membrane localization of EHD3, but has a dominant negative effect on its appearance in tubular ERC structures. Non-SUMOylated EHD3 delays transferrin recycling from the ERC to the cell surface. Our findings indicate that SUMOylation of EHD3 is involved in tubulation of the ERC membranes, which is important for efficient recycling.
authors.affiliation: Department of Cell Research and Immunology, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: Or
authors.initials: O
authors.lastname: Cabasso
authors.affiliation: Department of Cell Research and Immunology, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: Olga
authors.initials: O
authors.lastname: Pekar
authors.affiliation: Department of Cell Research and Immunology, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: Mia
authors.initials: M
authors.lastname: Horowitz
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002522:Chlorocebus aethiops; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D006801:Humans; D018613:Microscopy, Confocal; D058207:Sumoylation / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; C406447:EHD3 protein, human