title: Neuronal Galectin-4 is required for axon growth and for the organization of axonal membrane L1 delivery and clustering.
abstract: Axon membrane glycoproteins are essential for neuronal differentiation, although the mechanisms underlying their polarized sorting and organization are poorly understood. We describe here that galectin-4 (Gal-4), a lectin highly expressed in gastrointestinal tissues and involved in epithelial glycoprotein transport, is expressed by hippocampal and cortical neurons where it is sorted to discrete segments of the axonal membrane in a microtubule- and sulfatide-dependent manner. Gal-4 knockdown retards axon growth, an effect that can be rescued by recombinant Gal-4 addition. This Gal-4 reduction, as inhibition of sulfatide synthesis does, lowers the presence and clustered organization of axon growth-promoting molecule NCAM L1 at the axon membrane. Furthermore, we find that Gal-4 interacts with L1 by specifically binding to LacNAc branch ends of L1 N-glycans. Impairing the maturation of these N-glycans precludes Gal-4/L1 association resulting in a failure of L1 membrane cluster organization. In all, Gal-4 sorts to axon plasma membrane segments by binding to sulfatide-containing microtubule-associated carriers and being bivalent, it organizes the transport of L1, and likely other axonal glycoproteins, by attaching them to the carriers through their LacNAc termini. This mechanism would underlie L1 functional organization on the plasma membrane, required for proper axon growth.
authors: Membrane Biology and Axonal Repair Laboratory, Hospital Nacional de Parapléjicos (SESCAM), Finca La Peraleda s/n, Toledo, Spain.
authors: Silvia
authors: S
authors: Velasco
authors: Natalia
authors: N
authors: Díez-Revuelta
authors: Teresa
authors: T
authors: Hernández-Iglesias
authors: Herbert
authors: H
authors: Kaltner
authors: Sabine
authors: S
authors: André
authors: Hans-Joachim
authors: HJ
authors: Gabius
authors: José
authors: J
authors: Abad-Rodríguez
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D037541:Galectin 4 / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006624:Hippocampus / Q000166:cytology; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D037541:Galectin 4; D039842:Neural Cell Adhesion Molecule L1; D034741:RNA, Small Interfering