{"entity": "researcher", "timestamp": "2026-09-06T14:54:22.114Z", "family": "Schulte", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-2700-7013", "affiliations": [], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ca48082cc934a8494ac50e756be0f3e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ca48082cc934a8494ac50e756be0f3e"}}, "publications": [{"entity": "publication", "iuid": "a1f4420f0fe54419acb90d1042a2f9d7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a1f4420f0fe54419acb90d1042a2f9d7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a1f4420f0fe54419acb90d1042a2f9d7"}}, "title": "Pathway selectivity in Frizzleds is achieved by conserved micro-switches defining pathway-determining, active conformations.", "authors": [{"family": "Gr\u00e4tz", "given": "Lukas", "initials": "L", "orcid": "0000-0001-6755-0742", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/336fa12649bb40c99a66334c74a2a91b.json"}}, {"family": "Kowalski-Jahn", "given": "Maria", "initials": "M", "orcid": "0000-0003-1442-3656", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a23a8e0b2e8543b68098981fd39d97b6.json"}}, {"family": "Scharf", "given": "Magdalena M", "initials": "MM", "orcid": "0000-0002-3305-3956", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca43ba6516014fe597ead17e737f697a.json"}}, {"family": "Kozielewicz", "given": "Pawel", "initials": "P", "orcid": "0000-0003-1414-3566", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/961a43fbd1ef433ba2faace9d92cb73b.json"}}, {"family": "Jahn", "given": "Michael", "initials": "M", "orcid": "0000-0002-3913-153X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ce2ef4c47b24946876c12a549785e36.json"}}, {"family": "Bous", "given": "Julien", "initials": "J", "orcid": "0000-0002-3459-7592", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/435ffe2f8b11423f8d68fc41c0d4171c.json"}}, {"family": "Lambert", "given": "Nevin A", "initials": "NA", "orcid": "0000-0001-7550-0921", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/56c24f300f0142de983b18f22352e2fe.json"}}, {"family": "Gloriam", "given": "David E", "initials": "DE", "orcid": "0000-0002-4299-7561", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2d4cf683c6874e7782c68b00d38b926c.json"}}, {"family": "Schulte", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-2700-7013", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ca48082cc934a8494ac50e756be0f3e.json"}}], "type": "journal article", "published": "2023-07-29", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "14", "issue": "1", "pages": "4573", "issn-l": "2041-1723"}, "abstract": "The class Frizzled of G protein-coupled receptors (GPCRs), consisting of ten Frizzled (FZD1-10) paralogs and Smoothened, remains one of the most enigmatic GPCR families. This class mediates signaling predominantly through Disheveled (DVL) or heterotrimeric G proteins. However, the mechanisms underlying pathway selection are elusive. Here we employ a structure-driven mutagenesis approach in combination with an extensive panel of functional signaling readouts to investigate the importance of conserved state-stabilizing residues in FZD5 for signal specification. Similar data were obtained for FZD4 and FZD10 suggesting that our findings can be extrapolated to other members of the FZD family. Comparative molecular dynamics simulations of wild type and selected FZD5 mutants further support the concept that distinct conformational changes in FZDs specify the signal outcome. In conclusion, we find that FZD5 and FZDs in general prefer coupling to DVL rather than heterotrimeric G proteins and that distinct active state micro-switches in the receptor are essential for pathway selection arguing for conformational changes in the receptor protein defining transducer selectivity.", "doi": "10.1038/s41467-023-40213-0", "pmid": "37516754", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10387068"}, {"db": "pii", "key": "10.1038/s41467-023-40213-0"}], "notes": [], "created": "2026-08-21T11:49:27.881Z", "modified": "2026-08-21T11:49:28.228Z"}, {"entity": "publication", "iuid": "1ccddc0c63f34f59a08b278111e9dbef", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1ccddc0c63f34f59a08b278111e9dbef.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1ccddc0c63f34f59a08b278111e9dbef"}}, "title": "A conserved molecular switch in Class F receptors regulates receptor activation and pathway selection.", "authors": [{"family": "Wright", "given": "Shane C", "initials": "SC", "orcid": "0000-0002-7470-5068", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5bb883060bdc45ddb27b4d4f737de17e.json"}}, {"family": "Kozielewicz", "given": "Pawe\u0142", "initials": "P", "orcid": "0000-0003-1414-3566", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/961a43fbd1ef433ba2faace9d92cb73b.json"}}, {"family": "Kowalski-Jahn", "given": "Maria", "initials": "M"}, {"family": "Petersen", "given": "Julian", "initials": "J"}, {"family": "Bowin", "given": "Carl-Fredrik", "initials": "CF"}, {"family": "Slodkowicz", "given": "Greg", "initials": "G"}, {"family": "Marti-Solano", "given": "Maria", "initials": "M", "orcid": "0000-0003-0373-8927", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2724e93722494fb28214cbbe0bd8c499.json"}}, {"family": "Rodr\u00edguez", "given": "David", "initials": "D"}, {"family": "Hot", "given": "Belma", "initials": "B"}, {"family": "Okashah", "given": "Najeah", "initials": "N"}, {"family": "Strakova", "given": "Katerina", "initials": "K"}, {"family": "Valnohova", "given": "Jana", "initials": "J"}, {"family": "Babu", "given": "M Madan", "initials": "MM", "orcid": "0000-0003-0556-6196", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/86a83ee050b44075b722c6df37192df9.json"}}, {"family": "Lambert", "given": "Nevin A", "initials": "NA", "orcid": "0000-0001-7550-0921", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/56c24f300f0142de983b18f22352e2fe.json"}}, {"family": "Carlsson", "given": "Jens", "initials": "J"}, {"family": "Schulte", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-2700-7013", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ca48082cc934a8494ac50e756be0f3e.json"}}], "type": "journal article", "published": "2019-02-08", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "10", "issue": "1", "pages": "667"}, "abstract": "Class F receptors are considered valuable therapeutic targets due to their role in human disease, but structural changes accompanying receptor activation remain unexplored. Employing population and cancer genomics data, structural analyses, molecular dynamics simulations, resonance energy transfer-based approaches and mutagenesis, we identify a conserved basic amino acid in TM6 in Class F receptors that acts as a molecular switch to mediate receptor activation. Across all tested Class F receptors (FZD4,5,6,7, SMO), mutation of the molecular switch confers an increased potency of agonists by stabilizing an active conformation as assessed by engineered mini G proteins as conformational sensors. Disruption of the switch abrogates the functional interaction between FZDs and the phosphoprotein Dishevelled, supporting conformational selection as a prerequisite for functional selectivity. Our studies reveal the molecular basis of a common activation mechanism conserved in all Class F receptors, which facilitates assay development and future discovery of Class F receptor-targeting drugs.", "doi": "10.1038/s41467-019-08630-2", "pmid": "30737406", "labels": {"Jens Carlsson": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-019-08630-2"}, {"db": "pmc", "key": "PMC6368630"}], "notes": [], "created": "2020-09-29T13:54:35.809Z", "modified": "2022-11-04T11:32:16.780Z"}, {"entity": "publication", "iuid": "873ad32c940f488da2b140fbbcb63e69", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/873ad32c940f488da2b140fbbcb63e69.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/873ad32c940f488da2b140fbbcb63e69"}}, "title": "FZD5 is a G\u03b1q-coupled receptor that exhibits the functional hallmarks of prototypical GPCRs.", "authors": [{"family": "Wright", "given": "Shane C", "initials": "SC", "orcid": "0000-0002-7470-5068", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5bb883060bdc45ddb27b4d4f737de17e.json"}}, {"family": "Ca\u00f1izal", "given": "Maria Consuelo Alonso", "initials": "MCA", "orcid": "0000-0002-3030-8319", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a5732a6ca153402b9ca65f6b113099cd.json"}}, {"family": "Benkel", "given": "Tobias", "initials": "T", "orcid": "0000-0001-8701-2706", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0a3ba734e67342988b6fb58e4fb1d3d1.json"}}, {"family": "Simon", "given": "Katharina", "initials": "K"}, {"family": "Le Gouill", "given": "Christian", "initials": "C", "orcid": "0000-0002-6455-1800", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bebe017db6c249958e700170b51f1018.json"}}, {"family": "Matricon", "given": "Pierre", "initials": "P", "orcid": "0000-0001-9350-896X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/19dcd180ddc54eb48269a1638d83ece1.json"}}, {"family": "Namkung", "given": "Yoon", "initials": "Y", "orcid": "0000-0002-3085-2066", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9ab95b4d449a4a62876b405fdec6ded1.json"}}, {"family": "Lukasheva", "given": "Viktoria", "initials": "V", "orcid": "0000-0002-7364-0311", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4b2b46799ad4a08adb313a6dcee8481.json"}}, {"family": "K\u00f6nig", "given": "Gabriele M", "initials": "GM"}, {"family": "Laporte", "given": "St\u00e9phane A", "initials": "SA", "orcid": "0000-0002-0633-543X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ead9c152f3034af19ddcfccd42c308c1.json"}}, {"family": "Carlsson", "given": "Jens", "initials": "J"}, {"family": "Kostenis", "given": "Evi", "initials": "E", "orcid": "0000-0001-8284-5514", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6173cb94cd1f419e94dc544b443d954f.json"}}, {"family": "Bouvier", "given": "Michel", "initials": "M", "orcid": "0000-0003-1128-0100", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3cd88ee850114602a671892083323121.json"}}, {"family": "Schulte", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-2700-7013", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ca48082cc934a8494ac50e756be0f3e.json"}}, {"family": "Hoffmann", "given": "Carsten", "initials": "C", "orcid": "0000-0003-0884-9300", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3202233c9cf540ecac21d67ae3a08702.json"}}], "type": "journal article", "published": "2018-12-04", "journal": {"title": "Sci Signal", "issn": "1937-9145", "issn-l": "1945-0877", "volume": "11", "issue": "559", "pages": "eaar5536"}, "abstract": "Frizzleds (FZDs) are a group of seven transmembrane-spanning (7TM) receptors that belong to class F of the G protein-coupled receptor (GPCR) superfamily. FZDs bind WNT proteins to stimulate diverse signaling cascades involved in embryonic development, stem cell regulation, and adult tissue homeostasis. Frizzled 5 (FZD5) is one of the most studied class F GPCRs that promote the functional inactivation of the \u03b2-catenin destruction complex in response to WNTs. However, whether FZDs function as prototypical GPCRs has been heavily debated and, in particular, FZD5 has not been shown to activate heterotrimeric G proteins. Here, we show that FZD5 exhibited a conformational change after the addition of WNT-5A, which is reminiscent of class A and class B GPCR activation. In addition, we performed several live-cell imaging and spectrometric-based approaches, such as dual-color fluorescence recovery after photobleaching (dcFRAP) and resonance energy transfer (RET)-based assays that demonstrated that FZD5 activated G\u03b1q and its downstream effectors upon stimulation with WNT-5A. Together, these findings suggest that FZD5 is a 7TM receptor with a bona fide GPCR activation profile and suggest novel targets for drug discovery in WNT-FZD signaling.", "doi": "10.1126/scisignal.aar5536", "pmid": "30514810", "labels": {"Jens Carlsson": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "11/559/eaar5536"}], "notes": [], "created": "2020-09-29T13:54:34.686Z", "modified": "2022-11-04T11:32:17.011Z"}, {"entity": "publication", "iuid": "3cf6326eacfa4092a85508124ff44e24", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/3cf6326eacfa4092a85508124ff44e24.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/3cf6326eacfa4092a85508124ff44e24"}}, "title": "Dishevelled enables casein kinase 1-mediated phosphorylation of Frizzled 6 required for cell membrane localization.", "authors": [{"family": "Strakova", "given": "Katerina", "initials": "K"}, {"family": "Kowalski-Jahn", "given": "Maria", "initials": "M"}, {"family": "Gybel", "given": "Tomas", "initials": "T"}, {"family": "Valnohova", "given": "Jana", "initials": "J"}, {"family": "Dhople", "given": "Vishnu M", "initials": "VM"}, {"family": "Harnos", "given": "Jakub", "initials": "J"}, {"family": "Bernatik", "given": "Ondrej", "initials": "O"}, {"family": "Ganji", "given": "Ranjani Sri", "initials": "RS"}, {"family": "Zdrahal", "given": "Zbynek", "initials": "Z"}, {"family": "Mulder", "given": "Jan", "initials": "J"}, {"family": "Lindskog", "given": "Cecilia", "initials": "C"}, {"family": "Bryja", "given": "Vitezslav", "initials": "V", "orcid": "0000-0002-9136-5085", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1727f2bb33eb418eb3f700448c293f69.json"}}, {"family": "Schulte", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-2700-7013", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ca48082cc934a8494ac50e756be0f3e.json"}}], "type": "journal article", "published": "2018-11-30", "journal": {"title": "J Biol Chem", "issn": "1083-351X", "volume": "293", "issue": "48", "pages": "18477-18493", "issn-l": "0021-9258"}, "abstract": "Frizzleds (FZDs) are receptors for secreted lipoglycoproteins of the Wingless/Int-1 (WNT) family, initiating an important signal transduction network in multicellular organisms. FZDs are G protein-coupled receptors (GPCRs), which are well known to be regulated by phosphorylation, leading to specific downstream signaling or receptor desensitization. The role and underlying mechanisms of FZD phosphorylation remain largely unexplored. Here, we investigated the phosphorylation of human FZD6 Using MS analysis and a phospho-state- and -site-specific antibody, we found that Ser-648, located in the FZD6 C terminus, is efficiently phosphorylated by casein kinase 1 \u03f5 (CK1\u03f5) and that this phosphorylation requires the scaffolding protein Dishevelled (DVL). In an overexpression system, DVL1, -2, and -3 promoted CK1\u03f5-mediated FZD6 phosphorylation on Ser-648. This DVL activity required an intact DEP domain and FZD-mediated recruitment of this domain to the cell membrane. Substitution of the CK1\u03f5-targeted phosphomotif reduced FZD6 surface expression, suggesting that Ser-648 phosphorylation controls membrane trafficking of FZD6 Phospho-Ser-648 FZD6 immunoreactivity in human fallopian tube epithelium was predominantly apical, associated with cilia in a subset of epithelial cells, compared with the total FZD6 protein expression, suggesting that FZD6 phosphorylation contributes to asymmetric localization of receptor function within the cell and to epithelial polarity. Given the key role of FZD6 in planar cell polarity, our results raise the possibility that asymmetric phosphorylation of FZD6 rather than asymmetric protein distribution accounts for polarized receptor signaling.", "doi": "10.1074/jbc.RA118.004656", "pmid": "30309985", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6290145"}, {"db": "pii", "key": "S0021-9258(20)31158-3"}], "notes": [], "created": "2026-08-21T12:03:17.988Z", "modified": "2026-08-21T12:03:18.050Z"}]}