title: Functional interplay between ganglioside GM1 and cross-linking galectin-1 induces axon-like neuritogenesis via integrin-based signaling and TRPC5-dependent Ca²⁺ influx.
abstract: Axon-like neuritogenesis in neuroblastoma (NG108-15) cells and primary cerebellar granular neurons is furthered by the presence of ganglioside GM1. We describe here that galectin-1 (Gal-1), a homobivalent endogenous lectin, is an effector by cross-linking the ganglioside and its associated glycoprotein α5 β1 -integrin. The thereby triggered signaling cascade involves autophosphorylation of focal adhesion kinase and activation of phospholipase Cγ and phosphoinositide-3 kinase. This leads to a transient increase in the intracellular Ca(2+) concentration by opening of TRPC5 channels, which belong to the signal transduction-gated cation channels. Controls with GM1-defective cells (NG-CR72 and neurons from ganglio-series KO mice) were retarded in axonal growth, underscoring the relevance of GM1 as functional counterreceptor for Gal-1. The lectin's presence was detected in the NG108-15 cells, suggesting an autocrine mechanism of action, and in astrocytes in situ. Gal-1, as cross-linking lectin, can thus translate metabolic conversion of ganglioside GD1a to GM1 by neuraminidase action into axon growth. Galectin-1 (Gal-1) was shown an effector of axonogenesis in cerebellar granule neurons (CGNs) and NG108-15 cells by cross-linking GM1 ganglioside and its associated glycoprotein α5 β1 -integrin. The resulting signaling led to a transient increase in intracellular Ca(2+) by opening TRPC5 channels. CGNs deficient in GM1 showed retarded axonogenesis, underscoring the relevance of GM1 as functional counterreceptor for Gal-1 in this process. This Gal-1/GM1-induced signaling was manifest only at the earliest, initiating stage of axon development.
authors.affiliation: Department of Pharmacology, Physiology & Neurosciences, Rutgers-The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Gusheng
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Physiology & Neurosciences, Rutgers-The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Zi-Hua
authors.initials: ZH
authors.lastname: Lu
authors.affiliation: Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität, München, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: André
authors.affiliation: Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität, München, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gabius
authors.affiliation: Department of Pharmacology, Physiology & Neurosciences, Rutgers-The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Ledeen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology*; D001549:Benzamides / Q000493:pharmacokinetics; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005677:G(M1) Ganglioside / Q000235:genetics / Q000378:metabolism*; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000235:genetics*; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D013696:Temperature; D014443:Tyrosine / Q000031:analogs & derivatives / Q000493:pharmacokinetics
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D037483:Galectin 1; D016023:Integrins; D034741:RNA, Small Interfering; D050052:TRPC Cation Channels; C491780:TRPC5 protein, human; D005677:G(M1) Ganglioside; D014443:Tyrosine; C012614:1-nitrohydroxyphenyl-N-benzoylalanine; D002118:Calcium
keywords: Ca2+ level; axon growth; ganglioside; integrin; lectin; neuron