{"entity": "journal", "iuid": "ed7aba2a75f943a3b0a32742eed107bd", "timestamp": "2026-04-12T02:19:01.328Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/journal/Front%20Cell%20Dev%20Biol.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/journal/Front%20Cell%20Dev%20Biol"}}, "title": "Front Cell Dev Biol", "issn": "2296-634X", "issn-l": "2296-634X", "publications_count": 4, "publications": [{"entity": "publication", "iuid": "0c65c4d4b8ef4f05bcd889977e447fc3", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0c65c4d4b8ef4f05bcd889977e447fc3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0c65c4d4b8ef4f05bcd889977e447fc3"}}, "title": "Single-Molecule, Super-Resolution, and Functional Analysis of G Protein-Coupled Receptor Behavior Within the T Cell Immunological Synapse.", "authors": [{"family": "Felce", "given": "James H", "initials": "JH"}, {"family": "Parolini", "given": "Lucia", "initials": "L"}, {"family": "Sezgin", "given": "Erdinc", "initials": "E"}, {"family": "C\u00e9spedes", "given": "Pablo F", "initials": "PF"}, {"family": "Korobchevskaya", "given": "Kseniya", "initials": "K"}, {"family": "Jones", "given": "Mathew", "initials": "M"}, {"family": "Peng", "given": "Yanchun", "initials": "Y"}, {"family": "Dong", "given": "Tao", "initials": "T"}, {"family": "Fritzsche", "given": "Marco", "initials": "M"}, {"family": "Aarts", "given": "Dirk", "initials": "D"}, {"family": "Frater", "given": "John", "initials": "J"}, {"family": "Dustin", "given": "Michael L", "initials": "ML"}], "type": "journal article", "published": "2021-01-18", "journal": {"title": "Front Cell Dev Biol", "issn": "2296-634X", "volume": "8", "pages": "608484", "issn-l": "2296-634X"}, "abstract": "A central process in immunity is the activation of T cells through interaction of T cell receptors (TCRs) with agonistic peptide-major histocompatibility complexes (pMHC) on the surface of antigen presenting cells (APCs). TCR-pMHC binding triggers the formation of an extensive contact between the two cells termed the immunological synapse, which acts as a platform for integration of multiple signals determining cellular outcomes, including those from multiple co-stimulatory/inhibitory receptors. Contributors to this include a number of chemokine receptors, notably CXC-chemokine receptor 4 (CXCR4), and other members of the G protein-coupled receptor (GPCR) family. Although best characterized as mediators of ligand-dependent chemotaxis, some chemokine receptors are also recruited to the synapse and contribute to signaling in the absence of ligation. How these and other GPCRs integrate within the dynamic structure of the synapse is unknown, as is how their normally migratory G\u03b1i-coupled signaling is terminated upon recruitment. Here, we report the spatiotemporal organization of several GPCRs, focusing on CXCR4, and the G protein G\u03b1i2 within the synapse of primary human CD4+ T cells on supported lipid bilayers, using standard- and super-resolution fluorescence microscopy. We find that CXCR4 undergoes orchestrated phases of reorganization, culminating in recruitment to the TCR-enriched center. This appears to be dependent on CXCR4 ubiquitination, and does not involve stable interactions with TCR microclusters, as viewed at the nanoscale. Disruption of this process by mutation impairs CXCR4 contributions to cellular activation. G\u03b1i2 undergoes active exclusion from the synapse, partitioning from centrally-accumulated CXCR4. Using a CRISPR-Cas9 knockout screen, we identify several diverse GPCRs with contributions to T cell activation, most significantly the sphingosine-1-phosphate receptor S1PR1, and the oxysterol receptor GPR183. These, and other GPCRs, undergo organization similar to CXCR4; including initial exclusion, centripetal transport, and lack of receptor-TCR interactions. These constitute the first observations of GPCR dynamics within the synapse, and give insights into how these receptors may contribute to T cell activation. The observation of broad GPCR contributions to T cell activation also opens the possibility that modulating GPCR expression in response to cell status or environment may directly regulate responsiveness to pMHC.", "doi": "10.3389/fcell.2020.608484", "pmid": "33537301", "labels": {"SciLifeLab Fellow": null, "Erdinc Sezgin": null}, "xrefs": [{"db": "pmc", "key": "PMC7848080"}], "notes": [], "created": "2022-12-01T12:42:19.580Z", "modified": "2022-12-01T12:42:19.599Z"}, {"entity": "publication", "iuid": "8d03a5a2cade4b85affdc5f2dfd20a78", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8d03a5a2cade4b85affdc5f2dfd20a78.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8d03a5a2cade4b85affdc5f2dfd20a78"}}, "title": "Fluidity and Lipid Composition of Membranes of Peroxisomes, Mitochondria and the ER From Oleic Acid-Induced Saccharomyces cerevisiae", "authors": [{"family": "Reglinski", "given": "Katharina", "initials": "K"}, {"family": "Steinfort-Effelsberg", "given": "Laura", "initials": "L"}, {"family": "Sezgin", "given": "Erdinc", "initials": "E"}, {"family": "Klose", "given": "Christian", "initials": "C"}, {"family": "Platta", "given": "Harald W", "initials": "HW"}, {"family": "Girzalsky", "given": "Wolfgang", "initials": "W"}, {"family": "Eggeling", "given": "Christian", "initials": "C"}, {"family": "Erdmann", "given": "Ralf", "initials": "R"}], "type": "journal-article", "published": "2020-10-29", "journal": {"title": "Front Cell Dev Biol", "issn": "2296-634X", "issn-l": "2296-634X", "volume": "8", "issue": null, "pages": "574363"}, "abstract": "The maintenance of a fluid lipid bilayer is key for organelle function and cell viability. Given the critical role of lipid compositions in determining membrane properties and organelle identity, it is clear that cells must have elaborate mechanism for membrane maintenance during adaptive responses to environmental conditions. Emphasis of the presented study is on peroxisomes, oleic acid-inducible organelles that are essential for the growth of yeast under conditions of oleic acid as single carbon source. Here, we isolated peroxisomes, mitochondria and ER from oleic acid-induced Saccharomyces cerevisiae and determined the lipid composition of their membranes using shotgun lipidomics and compared it to lipid ordering using fluorescence microscopy. In comparison to mitochondrial and ER membranes, the peroxisomal membranes were slightly more disordered and characterized by a distinct enrichment of phosphaditylinositol, indicating an important role of this phospholipid in peroxisomal membrane associated processes.", "doi": "10.3389/fcell.2020.574363", "pmid": "33195209", "labels": {"Erdinc Sezgin": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC7658010"}], "notes": [], "created": "2020-11-05T16:13:51.241Z", "modified": "2022-11-04T11:32:14.179Z"}, {"entity": "publication", "iuid": "3ceb0778b0384ff6aa2c2b38816725ab", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/3ceb0778b0384ff6aa2c2b38816725ab.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/3ceb0778b0384ff6aa2c2b38816725ab"}}, "title": "More Favorable Palmitic Acid Over Palmitoleic Acid Modification of Wnt3 Ensures Its Localization and Activity in Plasma Membrane Domains.", "authors": [{"family": "Azbazdar", "given": "Yagmur", "initials": "Y"}, {"family": "Ozalp", "given": "Ozgun", "initials": "O"}, {"family": "Sezgin", "given": "Erdinc", "initials": "E"}, {"family": "Veerapathiran", "given": "Sapthaswaran", "initials": "S"}, {"family": "Duncan", "given": "Anna L", "initials": "AL"}, {"family": "Sansom", "given": "Mark S P", "initials": "MSP"}, {"family": "Eggeling", "given": "Christian", "initials": "C"}, {"family": "Wohland", "given": "Thorsten", "initials": "T"}, {"family": "Karaca", "given": "Ezgi", "initials": "E"}, {"family": "Ozhan", "given": "Gunes", "initials": "G"}], "type": "journal article", "published": "2019-11-15", "journal": {"title": "Front Cell Dev Biol", "issn": "2296-634X", "volume": "7", "issue": null, "pages": "281", "issn-l": "2296-634X"}, "abstract": "While the lateral organization of plasma membrane components has been shown to control binding of Wnt ligands to their receptors preferentially in the ordered membrane domains, the role of posttranslational lipid modification of Wnt on this selective binding is unknown. Here, we identify that the canonical Wnt is presumably acylated by palmitic acid, a saturated 16-carbon fatty acid, at a conserved serine residue. Acylation of Wnt3 is dispensable for its secretion and binding to Fz8 while it is essential for Wnt3's proper binding and domain-like diffusion in the ordered membrane domains. We further unravel that non-palmitoylated Wnt3 is unable to activate Wnt/\u03b2-catenin signaling either in zebrafish embryos or in mammalian cells. Based on these results, we propose that the lipidation of canonical Wnt, presumably by a saturated fatty acid, determines its competence in interacting with the receptors in the appropriate domains of the plasma membrane, ultimately keeping the signaling activity under control.", "doi": "10.3389/fcell.2019.00281", "pmid": "31803740", "labels": {"Erdinc Sezgin": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC6873803"}], "notes": [], "created": "2020-11-05T16:21:32.066Z", "modified": "2022-11-07T11:31:19.031Z"}, {"entity": "publication", "iuid": "2966f96a367b40fb9968f751dc29eaa4", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2966f96a367b40fb9968f751dc29eaa4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2966f96a367b40fb9968f751dc29eaa4"}}, "title": "New Challenges to Study Heterogeneity in Cancer Redox Metabolism.", "authors": [{"family": "Benfeitas", "given": "Rui", "initials": "R"}, {"family": "Uhlen", "given": "Mathias", "initials": "M"}, {"family": "Nielsen", "given": "Jens", "initials": "J"}, {"family": "Mardinoglu", "given": "Adil", "initials": "A"}], "type": "journal article", "published": "2017-07-11", "journal": {"title": "Front Cell Dev Biol", "issn": "2296-634X", "issn-l": "2296-634X", "volume": "5", "issue": null, "pages": "65"}, "abstract": "Reactive oxygen species (ROS) are important pathophysiological molecules involved in vital cellular processes. They are extremely harmful at high concentrations because they promote the generation of radicals and the oxidation of lipids, proteins, and nucleic acids, which can result in apoptosis. An imbalance of ROS and a disturbance of redox homeostasis are now recognized as a hallmark of complex diseases. Considering that ROS levels are significantly increased in cancer cells due to mitochondrial dysfunction, ROS metabolism has been targeted for the development of efficient treatment strategies, and antioxidants are used as potential chemotherapeutic drugs. However, initial ROS-focused clinical trials in which antioxidants were supplemented to patients provided inconsistent results, i.e., improved treatment or increased malignancy. These different outcomes may result from the highly heterogeneous redox responses of tumors in different patients. Hence, population-based treatment strategies are unsuitable and patient-tailored therapeutic approaches are required for the effective treatment of patients. Moreover, due to the crosstalk between ROS, reducing equivalents [e.g., NAD(P)H] and central metabolism, which is heterogeneous in cancer, finding the best therapeutic target requires the consideration of system-wide approaches that are capable of capturing the complex alterations observed in all of the associated pathways. Systems biology and engineering approaches may be employed to overcome these challenges, together with tools developed in personalized medicine. However, ROS- and redox-based therapies have yet to be addressed by these methodologies in the context of disease treatment. Here, we review the role of ROS and their coupled redox partners in tumorigenesis. Specifically, we highlight some of the challenges in understanding the role of hydrogen peroxide (H2O2), one of the most important ROS in pathophysiology in the progression of cancer. We also discuss its interplay with antioxidant defenses, such as the coupled peroxiredoxin/thioredoxin and glutathione/glutathione peroxidase systems, and its reducing equivalent metabolism. Finally, we highlight the need for system-level and patient-tailored approaches to clarify the roles of these systems and identify therapeutic targets through the use of the tools developed in personalized medicine.", "doi": "10.3389/fcell.2017.00065", "pmid": "28744456", "labels": {"Adil Mardinoglu": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC5504267"}], "notes": [], "created": "2020-09-25T13:43:35.689Z", "modified": "2022-11-04T11:32:18.738Z"}], "created": "2020-09-25T13:43:35.701Z", "modified": "2020-11-27T13:12:59.624Z"}