title: Specific recycling receptors are targeted to the immune synapse by the intraflagellar transport system.
abstract: T cell activation requires sustained signaling at the immune synapse, a specialized interface with the antigen-presenting cell (APC) that assembles following T cell antigen receptor (TCR) engagement by major histocompatibility complex (MHC)-bound peptide. Central to sustained signaling is the continuous recruitment of TCRs to the immune synapse. These TCRs are partly mobilized from an endosomal pool by polarized recycling. We have identified IFT20, a component of the intraflagellar transport (IFT) system that controls ciliogenesis, as a central regulator of TCR recycling to the immune synapse. Here, we have investigated the interplay of IFT20 with the Rab GTPase network that controls recycling. We found that IFT20 forms a complex with Rab5 and the TCR on early endosomes. IFT20 knockdown (IFT20KD) resulted in a block in the recycling pathway, leading to a build-up of recycling TCRs in Rab5(+) endosomes. Recycling of the transferrin receptor (TfR), but not of CXCR4, was disrupted by IFT20 deficiency. The IFT components IFT52 and IFT57 were found to act together with IFT20 to regulate TCR and TfR recycling. The results provide novel insights into the mechanisms that control TCR recycling and immune synapse assembly, and underscore the trafficking-related function of the IFT system beyond ciliogenesis.
authors.affiliation: Department of Life Sciences, University of Siena, 53100 Siena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Finetti
authors.forename: Laura
authors.initials: L
authors.lastname: Patrussi
authors.forename: Giulia
authors.initials: G
authors.lastname: Masi
authors.forename: Anna
authors.initials: A
authors.lastname: Onnis
authors.forename: Donatella
authors.initials: D
authors.lastname: Galgano
authors.forename: Orso Maria
authors.initials: OM
authors.lastname: Lucherini
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Pazour
authors.forename: Cosima T
authors.initials: CT
authors.lastname: Baldari
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000938:Antigen-Presenting Cells / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D019169:Jurkat Cells; D008856:Microscopy, Fluorescence; D011485:Protein Binding / Q000235:genetics; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013569:Synapses / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C487991:IFT20 protein, human; C499179:IFT57 protein, human; D011948:Receptors, Antigen, T-Cell; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins
keywords: Immune synapse; Intraflagellar transport; Rab GTPases; Receptor recycling; Receptor sorting