Functional interplay between ganglioside GM1 and cross‐linking galectin‐1 induces axon‐like neuritogenesis via integrin‐based signaling and TRPC5‐dependent Ca2+ influx

• Published in: Journal of neurochemistry Vol. 136; no. 3; pp. 550 - 563
• Main Authors: Wu, Gusheng, Lu, Zi‐Hua, André, Sabine, Gabius, Hans‐Joachim, Ledeen, Robert W.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.02.2016; John Wiley and Sons Inc
• Subjects: Animals; Animals, Newborn; axon growth; Axons - physiology; Benzamides - pharmacokinetics; Ca2+ level; Calcium - metabolism; Cells, Cultured; Cerebellum - cytology; Enzyme Inhibitors - pharmacology; G(M1) Ganglioside - genetics; G(M1) Ganglioside - metabolism; Galectin 1 - genetics; Galectin 1 - metabolism; ganglioside; Gene Expression Regulation - genetics; integrin; Integrins - genetics; Integrins - metabolism; lectin; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurochemistry; neuron; Original; ORIGINAL ARTICLES; Protein Binding - drug effects; Protein Binding - genetics; Rats; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Signal Transduction - genetics; Temperature; TRPC Cation Channels - genetics; TRPC Cation Channels - metabolism; Tyrosine - analogs & derivatives; Tyrosine - pharmacokinetics; neuron; Ca2+ level; integrin; axon growth; lectin; ganglioside
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.13418

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 α5β1‐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 Ca2+ 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 α5β1‐integrin. The resulting signaling led to a transient increase in intracellular Ca2+ 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. 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 α5β1‐integrin. The resulting signaling led to a transient increase in intracellular Ca2+ 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.