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Cambridge Institute for Medical Research

 

Optineurin is a multifunctional protein important in autophagy and regulation of immune signalling. Defects in optineurin gene function are linked to a number of human diseases including motor neuron disease. Dr Thomas O’Loughlin and CIMR colleagues from the Buss lab, together with collaborators from UCL have shown in the Journal of Cell Science that downstream of a signal from viral RNA, optineurin moves to distinct foci close to the Golgi complex. This process results in the downregulation of the NFκB and IRF3 pathways, inflammatory cytokine secretion, and therefore a reduced immune response. Ultrastructural analysis of these foci reveals that this compartment consists of a tight cluster of small membrane vesicles, which appear positive for the autophagy protein ATG9A. Functional proteomics identifies part of the machinery sequestered at this viral RNA-induced compartment, while the cellular impact of disease-causing mutations in optineurin are also described.