title: Ubiquitination and endocytosis of the high affinity receptor for IgE.
abstract: The high affinity receptor for IgE (FcvarepsilonRI) is constitutivelly expressed on the surface of mast cells and basophils as a multimeric complex. Upon antigen ligation to FcvarepsilonRI-bound IgE molecules, the receptor complex transduces intracellular signals leading to the release of preformed and newly synthesised pro-inflammatory mediators. FcvarepsilonRI engagement also generates negative intracellular signals involving the coordinated action of adapters, phosphatases and ubiquitin ligases that limits the intensity and duration of positive signals. Relevant to this, antigen-induced FcvarepsilonRI ubiquitination has become recognized as an important signal for the internalization and delivery of engaged receptor complexes to lysosomes for degradation. In this article, we review recent advances in our understanding of molecular mechanisms that guarantee the clearance of antigen-stimulated FcvarepsilonRI complexes from the cell surface. A particular emphasis will be given on how lipid rafts and the ubiquitin pathway cooperate to ensure receptor internalization and sorting along the endocytic compartments. A brief discussion regarding how ubiquitination regulates the endocytosis of Fc receptors other than FcvarepsilonRI will be included.
authors.affiliation: Department of Experimental Medicine, Institute Pasteur-Fondazione Cenci Bolognetti, Sapienza University, 00161 Rome, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Molfetta
authors.forename: Francesca
authors.initials: F
authors.lastname: Gasparrini
authors.forename: Angela
authors.initials: A
authors.lastname: Santoni
authors.forename: Rossella
authors.initials: R
authors.lastname: Paolini
mesh_terms: D000818:Animals; D001491:Basophils / Q000378:metabolism; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D015536:Down-Regulation; D004705:Endocytosis / Q000502:physiology*; D025461:Feedback, Physiological; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism; D021962:Membrane Microdomains; D051379:Mice; D011499:Protein Processing, Post-Translational; D051381:Rats; D017455:Receptors, IgE / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D017455:Receptors, IgE