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We describe here that galectin\u20101 (Gal\u20101), a homobivalent endogenous lectin, is an effector by cross\u2010linking the ganglioside and its associated glycoprotein \u03b1<jats:sub>5<\/jats:sub>\u03b2<jats:sub>1<\/jats:sub>\u2010integrin. The thereby triggered signaling cascade involves autophosphorylation of focal adhesion kinase and activation of phospholipase C\u03b3 and phosphoinositide\u20103 kinase. This leads to a transient increase in the intracellular Ca<jats:sup>2+<\/jats:sup> concentration by opening of <jats:styled-content style=\"fixed-case\">TRPC<\/jats:styled-content>5 channels, which belong to the signal transduction\u2010gated cation channels. Controls with <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content>1\u2010defective cells (<jats:styled-content style=\"fixed-case\">NG<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>72 and neurons from ganglio\u2010series <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mice) were retarded in axonal growth, underscoring the relevance of <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content>1 as functional counterreceptor for Gal\u20101. The lectin's presence was detected in the <jats:styled-content style=\"fixed-case\">NG<\/jats:styled-content>108\u201015 cells, suggesting an autocrine mechanism of action, and in astrocytes <jats:italic>in\u00a0situ<\/jats:italic>. Gal\u20101, as cross\u2010linking lectin, can thus translate metabolic conversion of ganglioside <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content>1a to <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content>1 by neuraminidase action into axon growth.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13418-fig-0010-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nGalectin\u20101 (Gal\u20101) was shown an effector of axonogenesis in cerebellar granule neurons (CGNs) and NG108\u201015 cells by cross\u2010linking GM1 ganglioside and its associated glycoprotein \u03b1<jats:sub>5<\/jats:sub>\u03b2<jats:sub>1<\/jats:sub>\u2010integrin. The resulting signaling led to a transient increase in intracellular Ca<jats:sup>2+<\/jats:sup> by opening TRPC5 channels. CGNs deficient in GM1 showed retarded axonogenesis, underscoring the relevance of GM1 as functional counterreceptor for Gal\u20101 in this process. This Gal\u20101\/GM1\u2010induced signaling was manifest only at the earliest, initiating stage of axon development.\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13418","type":"journal-article","created":{"date-parts":[[2015,11,3]],"date-time":"2015-11-03T07:59:27Z","timestamp":1446537567000},"page":"550-563","source":"Crossref","is-referenced-by-count":43,"title":["Functional interplay between ganglioside <scp>GM<\/scp>1 and cross\u2010linking galectin\u20101 induces axon\u2010like neuritogenesis via integrin\u2010based signaling and <scp>TRPC<\/scp>5\u2010dependent Ca<sup>2+<\/sup> influx"],"prefix":"10.1111","volume":"136","author":[{"given":"Gusheng","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Physiology &amp; Neurosciences Rutgers\u2010The State University of New Jersey New Jersey Medical School Newark New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zi\u2010Hua","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology &amp; Neurosciences Rutgers\u2010The State University of New Jersey New Jersey Medical School Newark New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Andr\u00e9","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Physiologische Chemie Tier\u00e4rztliche Fakult\u00e4t Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans\u2010Joachim","family":"Gabius","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Physiologische Chemie Tier\u00e4rztliche Fakult\u00e4t Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert W.","family":"Ledeen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology &amp; Neurosciences Rutgers\u2010The State University of New Jersey New Jersey Medical School Newark New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,12,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2015.03.015"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"8387","DOI":"10.1523\/JNEUROSCI.21-21-08387.2001","article-title":"Plasma membrane ganglioside sialidase regulates axonal growth and regeneration in hippocampal neurons in culture","volume":"21","author":"Abad\u2010Rodr\u00edguez J.","year":"2001","journal-title":"J.\u00a0Neurosci."},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.12001"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-0186(83)90043-8"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004320050303"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/B307802G"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20699"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2007.05851.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules20021788"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00266629"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2001.tb00377.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1523\/JNEUROSCI.14-04-02272.1994","article-title":"Endogenous ganglioside GM1 modulates L\u2010type calcium channel activity in N18 neuroblastoma cells","volume":"14","author":"Carlson R. 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