title: The ectodomain of TLR3 receptor is required for its plasma membrane translocation.
abstract: Toll-like receptor 3 (TLR3) is a dsRNA sensing receptor that is localized in the cellular compartments but also at the plasma membrane. Overexpression of UNC93B1 promoted localization of TLR3, but not other nucleic acid sensing TLRs, to the plasma membrane. Here we show that UNC93B1 itself is localized at the plasma membrane. We investigated the role of different domains of TLR3 on cell signaling by preparing chimeric receptors between TLR3 and TLR9 where each of the transmembrane segments or cytosolic domains has been exchanged. While the ectodomain completely governs ligand specificity and the cytosolic TIR domain determines the engagement of the signaling adapters as well as the potentiation of receptor activation by UNC93B1, the ectodomain but not transmembrane segment or cytosolic domain determines plasma membrane localization of TLR3. Nevertheless, TLR3 receptor and ligand endocytosis as well as endosomal acidification are important for the robust signaling of TLR3.
authors.affiliation: National Institute of Chemistry, Hajdrihova 19, Ljubljana, Slovenia.
authors.forename: Jelka
authors.initials: J
authors.lastname: Pohar
authors.affiliation: National Institute of Chemistry, Hajdrihova 19, Ljubljana, Slovenia.
authors.forename: Nina
authors.initials: N
authors.lastname: Pirher
authors.affiliation: National Institute of Chemistry, Hajdrihova 19, Ljubljana, Slovenia; EN-FIST Centre of Excellence, Ljubljana, Slovenia.
authors.forename: Mojca
authors.initials: M
authors.lastname: Benčina
authors.affiliation: National Institute of Chemistry, Hajdrihova 19, Ljubljana, Slovenia; EN-FIST Centre of Excellence, Ljubljana, Slovenia.
authors.forename: Mateja
authors.initials: M
authors.lastname: Manček-Keber
authors.affiliation: National Institute of Chemistry, Hajdrihova 19, Ljubljana, Slovenia; EN-FIST Centre of Excellence, Ljubljana, Slovenia; Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Roman
authors.initials: R
authors.lastname: Jerala
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D008247:Lysosomes / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D011070:Poly I-C / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D051196:Toll-Like Receptor 3 / Q000737:chemistry* / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000737:chemistry / Q000378:metabolism
chemical_list: D008024:Ligands; D026901:Membrane Transport Proteins; D011993:Recombinant Fusion Proteins; C495344:TLR3 protein, human; C495371:TLR9 protein, human; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9; C454130:UNC93B1 protein, human; D011070:Poly I-C