2. Academic Validation
  3. The Vici syndrome protein EPG5 regulates intracellular nucleic acid trafficking linking autophagy to innate and adaptive immunity

The Vici syndrome protein EPG5 regulates intracellular nucleic acid trafficking linking autophagy to innate and adaptive immunity

  • Autophagy. 2018;14(1):22-37. doi: 10.1080/15548627.2017.1389356.
E Piano Mortari 1,  V Folgiero 2,  V Marcellini 1,  P Romania 2,  E Bellacchio 3,  V D'Alicandro 2,  C Bocci 1,  R Carrozzo 4,  D Martinelli 3,  S Petrini 5,  E Axiotis 1,  C Farroni 1,  F Locatelli 2 6,  U Schara 7,  D T Pilz 8,  H Jungbluth 9 10 11,  C Dionisi-Vici 3,  R Carsetti 1
Affiliations

Affiliations

  • 1 a B cell Physiopathology Unit , Immunology Research Area, IRCCS Bambino Gesù Children's Hospital , Rome , Italy.
  • 2 b Department of Pediatric Hematology and Oncology , IRCCS Bambino Gesù Children's Hospital , Rome , Italy.
  • 3 d Division of Metabolism , IRCCS Bambino Gesù Children's Hospital , Rome , Italy.
  • 4 e Unit for Neuromuscular and Neurodegenerative Diseases , IRCCS Bambino Gesù Children's Hospital , Rome , Italy.
  • 5 f Confocal Microscopy core facility , IRCCS Bambino Gesù Children's Hospital , Rome , Italy.
  • 6 c Department of Pediatric Science , University of Pavia , Pavia , Italy.
  • 7 h 41 Pediatric Neurology , University Childrens Hospital, University of Duisburg-Essen , Essen , Germany.
  • 8 i West of Scotland Genetics Service, Queen Elizabeth University Hospital , Glasgow G51 4TF , UK.
  • 9 g Department of Paediatric Neurology , Neuromuscular Service, Evelina's Children Hospital, Guy's and St. Thomas' Hospital NHS Foundation Trust , London , UK.
  • 10 j Randall Division for Cell and Molecular Biophysics , Muscle Signalling Section, King's College , London , UK.
  • 11 k Department of Basic and Clinical Neuroscience , IoPPN, King's College , London , UK.
PMID: 29130391 DOI: 10.1080/15548627.2017.1389356
Abstract

Vici syndrome is a human inherited multi-system disorder caused by recessive mutations in EPG5, encoding the EPG5 protein that mediates the fusion of autophagosomes with lysosomes. Immunodeficiency characterized by lack of memory B cells and increased susceptibility to Infection is an integral part of the condition, but the role of EPG5 in the immune system remains unknown. Here we show that EPG5 is indispensable for the transport of the TLR9 ligand CpG to the late endosomal-lysosomal compartment, and for TLR9-initiated signaling, a step essential for the survival of human memory B cells and their ultimate differentiation into plasma cells. Moreover, the predicted structure of EPG5 includes a membrane remodeling domain and a karyopherin-like domain, thus explaining its function as a carrier between separate vesicular compartments. Our findings indicate that EPG5, by controlling nucleic acids intracellular trafficking, links macroautophagy/Autophagy to innate and adaptive immunity.

Keywords

EPG5; Endosomal trafficking; TLR9; Vici syndrome; memory B cells.

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