Regulation of NKG2D Expression and Signaling by Endocytosis.
NKG2D is an activating receptor that can bind to a large number of stress-induced ligands that are expressed in the context of cancer or viral infection. This receptor is expressed on many cytotoxic lymphocytes, and plays a crucial role in antitumor and antiviral immune responses. However, exposure to NKG2D ligand-expressing target cells promotes receptor endocytosis, ultimately leading to lysosomal receptor degradation and impairment of NKG2D-mediated functions. Interestingly, before being degraded, internalized receptors can signal from the endosomal compartment, leading to the appropriate activation of cellular functional programs. This review summarizes recent findings on ligand-induced receptor internalization, with particular emphasis on the role of endocytosis in the control of both NKG2D-mediated intracellular signaling and receptor degradation.
Department of Molecular Medicine, Institute Pasteur-Fondazione Cenci Bolognetti, 'Sapienza' University of Rome, 00161, Rome, Italy.
Rosa
R
Molfetta
Department of Molecular Medicine, Institute Pasteur-Fondazione Cenci Bolognetti, 'Sapienza' University of Rome, 00161, Rome, Italy.
Linda
L
Quatrini
Department of Molecular Medicine, Institute Pasteur-Fondazione Cenci Bolognetti, 'Sapienza' University of Rome, 00161, Rome, Italy.
Beatrice
B
Zitti
Department of Experimental Medicine, 'Sapienza' University of Rome, 00161 Rome, Italy.
Cristina
C
Capuano
Department of Experimental Medicine, 'Sapienza' University of Rome, 00161 Rome, Italy.
Ricciarda
R
Galandrini
Department of Molecular Medicine, Institute Pasteur-Fondazione Cenci Bolognetti, 'Sapienza' University of Rome, 00161, Rome, Italy; Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS), Neuromed, Pozzilli, IS, Italy. Electronic address: angela.santoni@uniroma1.it.
Angela
A
Santoni
Department of Molecular Medicine, Institute Pasteur-Fondazione Cenci Bolognetti, 'Sapienza' University of Rome, 00161, Rome, Italy. Electronic address: rossella.paolini@uniroma1.it.
Rossella
R
Paolini
D000818:Animals; D004705:Endocytosis / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000276:immunology*; D011940:Receptor Aggregation; D015398:Signal Transduction / Q000276:immunology; D013312:Stress, Physiological; D014777:Virus Diseases / Q000276:immunology*
D055655:NK Cell Lectin-Like Receptor Subfamily K