{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T01:48:57Z","timestamp":1783648137037,"version":"3.55.0"},"reference-count":37,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,5,15]]},"abstract":"<jats:p>GDNF (glial cell-line-derived neurotrophic factor), and the closely related cytokines artemin and neurturin, bind strongly to heparin. Deletion of a basic amino-acid-rich sequence of 16 residues N-terminal to the first cysteine of the transforming growth factor \u03b2 domain of GDNF results in a marked reduction in heparin binding, whereas removal of a neighbouring sequence, and replacement of pairs of other basic residues with alanine had no effect. The heparin-binding sequence is quite distinct from the binding site for the high affinity GDNF polypeptide receptor, GFR\u03b11 (GDNF family receptor \u03b11), and heparin-bound GDNF is able to bind GFR\u03b11 simultaneously. The heparin-binding sequence of GDNF is dispensable both for GFR\u03b11 binding, and for activity for in vitro neurite outgrowth assay. Surprisingly, the observed inhibition of GDNF bioactivity with the wild-type protein in this assay was still found with the deletion mutant lacking the heparin-binding sequence. Heparin neither inhibits nor potentiates GDNF\u2013GFR\u03b11 interaction, and the extracellular domain of GFR\u03b11 does not bind to heparin itself, precluding heparin cross-bridging of cytokine and receptor polypeptides. The role of heparin and heparan sulfate in GDNF signalling remains unclear, but the present study indicates that it does not occur in the first step of the pathway, namely GDNF\u2013GFR\u03b11 engagement.<\/jats:p>","DOI":"10.1042\/bj20061747","type":"journal-article","created":{"date-parts":[[2007,4,27]],"date-time":"2007-04-27T08:02:48Z","timestamp":1177660968000},"page":"131-140","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["The major determinant of the heparin binding of glial cell-line-derived neurotrophic factor is near the N-terminus and is dispensable for receptor binding"],"prefix":"10.1042","volume":"404","author":[{"given":"Ivan","family":"Alfano","sequence":"first","affiliation":[{"name":"School of Biological Sciences, Royal Holloway University of London, Egham Hill, Egham, Surrey TW20 OEX, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parvez","family":"Vora","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Royal Holloway University of London, Egham Hill, Egham, Surrey TW20 OEX, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary\u00a0S.","family":"Mummery","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Royal Holloway University of London, Egham Hill, Egham, Surrey TW20 OEX, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Mulloy","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Structure, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Herts EN6 3QC, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher\u00a0C.","family":"Rider","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Royal Holloway University of London, Egham Hill, Egham, Surrey TW20 OEX, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2007,4,26]]},"reference":[{"key":"2021112213180714300_B1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0959-4388(99)00048-3","article-title":"The GDNF family ligands and receptors: implications for neural development","volume":"10","author":"Baloh","year":"2000","journal-title":"Curr. 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