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We demonstrated that UNC-5 and UNC-6\/netrin form a large, stable, and rigid complex in the presence of heparin, and heparin and UNC-5 exclude the attractive UNC-40\/DCC receptor from binding to UNC-6\/netrin to a large extent.\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    with a heparin-binding\u2013deficient UNC-5 fail to establish proper gonad morphology due to abrogated cell migration, which relies on repulsive UNC-5 signaling in response to UNC-6. Combining UNC-5 mutations targeting heparin and UNC-6\/netrin contacts results in complete cell migration and axon guidance defects. Our findings establish repulsive netrin responses to be mediated through a glycosaminoglycan-regulated macromolecular complex.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adj8083","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T13:59:17Z","timestamp":1708091957000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":11,"title":["Structural insights into the formation of repulsive netrin guidance complexes"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7511-6284","authenticated-orcid":true,"given":"Jessica M.","family":"Priest","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA."},{"name":"Institute for Neuroscience, University of Chicago, Chicago, IL 60637, USA."},{"name":"Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, 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