title: Cell-surface localization of Pellino antagonizes Toll-mediated innate immune signalling by controlling MyD88 turnover in Drosophila.
abstract: Innate immunity mediated by Toll signalling has been extensively studied, but how Toll signalling is precisely controlled in balancing innate immune responses remains poorly understood. It was reported that the plasma membrane localization of Drosophila MyD88 is necessary for the recruitment of cytosolic adaptor Tube to the cell surface, thus contributing to Toll signalling transduction. Here we demonstrate that Drosophila Pellino functions as a negative regulator in Toll-mediated signalling. We show that Pellino accumulates at the plasma membrane upon the activation of Toll signalling in a MyD88-dependent manner. Moreover, we find that Pellino is associated with MyD88 via its CTE domain, which is necessary and sufficient to promote Pellino accumulation at the plasma membrane where it targets MyD88 for ubiquitination and degradation. Collectively, our study uncovers a mechanism by which a feedback regulatory loop involving MyD88 and Pellino controls Toll-mediated signalling, thereby maintaining homeostasis of host innate immunity.
authors.affiliation: 1] State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [3].
authors.forename: Shanming
authors.initials: S
authors.lastname: Ji
authors.affiliation: 1] State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2].
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.affiliation: 1] Centre for Computational and Evolutionary Biology, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101, China [2].
authors.forename: Xiudeng
authors.initials: X
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: 1] State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Dahua
authors.initials: D
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Qinmiao
authors.initials: Q
authors.lastname: Sun
mesh_terms: D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D007113:Immunity, Innate / Q000502:physiology; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors