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

E. Piano Mortari, V. Folgiero, V. Marcellini, P. Romania, E. Bellacchio, V. D'Alicandro, C. Bocci, R. Carrozzo, D. Martinelli, S. Petrini, E. Axiotis, C. Farroni, Franco Locatelli, U. Schara, D. T. Pilz, H. Jungbluth, C. Dionisi-Vici, R. Carsetti

Risultato della ricerca: Contributo in rivistaArticolo in rivista

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.
Lingua originaleEnglish
pagine (da-a)22-37
Numero di pagine16
RivistaAutophagy
Volume14
DOI
Stato di pubblicazionePubblicato - 2018

Keywords

  • EPG5
  • Endosomal trafficking
  • TLR9
  • Vici syndrome
  • memory B cells

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