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Sorting nexin 27 (SNX27) association to the retromer complex mediates intracellular trafficking of cargoes containing PSD95/Dlg1/ZO-1 (PDZ)-binding C-terminal sequences from endosomes to the cell surface, preventing their lysosomal degradation. Antigen recognition by T lymphocyte leads to the formation of a highly organized structure named the immune synapse (IS), which ensures cell-cell communication and sustained T cell activation. At the neuronal synapse, SNX27 recycles PDZ-binding receptors and its defective expression is associated with synaptic dysfunction and cognitive impairment. In T lymphocytes, SNX27 was found localized at recycling endosomal compartments that polarized to the IS, suggesting a function in polarized traffic to this structure. Proteomic analysis of PDZ-SNX27 interactors during IS formation identify proteins with known functions in cytoskeletal reorganization and lipid regulation, such as diacylglycerol (DAG) kinase (DGK) ζ, as well as components of the retromer and WASH complex. In this study, we investigated the consequences of SNX27 deficiency in cytoskeletal reorganization during IS formation. Our analyses demonstrate that SNX27 controls the polarization towards the cell-cell interface of the PDZ-interacting cargoes DGKζ and the retromer subunit vacuolar protein sorting protein 26, among others. SNX27 silencing abolishes the formation of a DAG gradient at the IS and prevents re-localization of the dynactin complex component dynactin-1/p150Glued, two events that correlate with impaired microtubule organizing center translocation (MTOC). SNX27 silenced cells show marked alteration in cytoskeleton organization including a failure in the organization of the microtubule network and defects in actin clearance at the IS. Reduced SNX27 expression was also found to hinder the arrangement of signaling microclusters at the IS, as well as the polarization of the secretory machinery towards the antigen presenting cells. Our results broaden the knowledge of SNX27 function in T lymphocytes by showing a function in modulating IS organization through regulated trafficking of cargoes.

The investigation, and ultimate application, of topological insulators, typically involve exposure to ambient conditions or their integration with metals, which lead to surface oxidation or material intermixing. X-ray photoelectron spectroscopy (XPS) measurements that demonstrate passivated and intermixing-free interfaces in the topological insulator BiTe by means of dry-transferred CVD graphene are reported. After air exposure, no traces of BiTe oxidation are found. Furthermore, it is demonstrated that graphene acts as a very efficient metal and chalcogen diffusion barrier in BiTe/graphene/permalloy (Py) heterostructures, which are relevant for spintronics. Such results are in stark contrast with the significant surface degradation observed in bare BiTe under ambient conditions and the deep Bi-Te bonding disruption that occurs in BiTe/Py heterostructures. These findings provide a new approach to control and engineer topological insulator interfaces for spintronic applications and a new platform to investigate the combined use of graphene and topological insulator Dirac states., The authors acknowledge the support of the Spanish Research Agency (AEI), Ministry of Science and Innovation (MCIN) under contract no. PID2019-111773RB-I00/AEI/10.13039/501100011033, PGC2018-095032-B-100, and SEV-2017-0706 Severo Ochoa, and by PCI2021-122035-2A funded by MICIN and by the European Union Next Generation EU/PRTR, and of the European Union's Horizon 2020 under grant agreement 881603 (Graphene Flagship). R.G. acknowledges funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 840588 (GRISOTO) and I.F.A from a fellowship from la Caixa Foundation (ID 100010434) with code LCF/BQ/DI18/11660030 and of H2020 Marie Skłodowska-Curie grant agreement No. 713673. J.F.S acknowledges support from MINECO under contract RYC2019-028368-I/AEI/10.13039/50110001103.