{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:38:54Z","timestamp":1790343534577,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T00:00:00Z","timestamp":1701907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["125440785\u2010SFB877\u2010A10"],"award-info":[{"award-number":["125440785\u2010SFB877\u2010A10"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:p>\n                    Interleukin\u201011 (IL\u201011) is a member of the IL\u20106 family of cytokines and is an important factor for bone homeostasis. IL\u201011 binds to and signals via the membrane\u2010bound IL\u201011 receptor (IL\u201011R, classic signaling) or soluble forms of the IL\u201011R (sIL\u201011R, trans\u2010signaling). Mutations in the\n                    <jats:italic>IL11RA<\/jats:italic>\n                    gene, which encodes the IL\u201011R, are associated with craniosynostosis, a human condition in which one or several of the sutures close prematurely, resulting in malformation of the skull. The biological mechanisms of how mutations within the IL\u201011R are linked to craniosynostosis are mostly unexplored. In this study, we analyze two variants of the IL\u201011R described in craniosynostosis patients: p.T306_S308dup, which results in a duplication of three amino\u2010acid residues within the membrane\u2010proximal fibronectin type III domain, and p.E364_V368del, which results in a deletion of five amino\u2010acid residues in the so\u2010called stalk region adjacent to the plasma membrane. The stalk region connects the three extracellular domains to the transmembrane and intracellular region of the IL\u201011R and contains cleavage sites for different proteases that generate sIL\u201011R variants. Using a combination of bioinformatics and different biochemical, molecular, and cell biology methods, we show that the IL\u201011R\u2010T306_S308dup variant does not mature correctly, is intracellularly retained, and does not reach the cell surface. In contrast, the IL\u201011R\u2010E364_V368del variant is fully biologically active and processed normally by proteases, thus allowing classic and trans\u2010signaling of IL\u201011. Our results provide evidence that mutations within the\n                    <jats:italic>IL11RA<\/jats:italic>\n                    gene may not be causative for craniosynostosis and suggest that other regulatory mechanism(s) are involved but remain to be identified.\n                  <\/jats:p>","DOI":"10.1111\/febs.17015","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T10:29:37Z","timestamp":1700735377000},"page":"1667-1683","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Molecular characterization of the craniosynostosis\u2010associated interleukin\u201011 receptor variants p.T306_S308dup and p.E364_V368del"],"prefix":"10.1111","volume":"291","author":[{"given":"Birte","family":"Kespohl","sequence":"first","affiliation":[{"name":"Department of Pathology, Medical Faculty Otto\u2010von\u2010Guericke\u2010University Magdeburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna\u2010Lena","family":"Hegele","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical Faculty Otto\u2010von\u2010Guericke\u2010University Magdeburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"D\u00fcsterh\u00f6ft","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pharmacology RWTH Aachen University  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1364-9154","authenticated-orcid":false,"given":"Hans","family":"Bakker","sequence":"additional","affiliation":[{"name":"Institute of Clinical Biochemistry Hannover Medical School  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falk F. 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