title: Syntaxin 1 is required for DCC/Netrin-1-dependent chemoattraction of migrating neurons from the lower rhombic lip.
abstract: Directed cell migration and axonal guidance are essential steps in neural development that share many molecular mechanisms. The guidance of developing axons and migrating neurons is likely to depend on the precise control of plasmalemma turnover in selected regions of leading edges and growth cones, respectively. Previous results provided evidence of a signaling mechanism that couples chemotropic deleted in colorectal cancer (DCC)/Netrin-1 axonal guidance and exocytosis through Syntaxin1(Sytx1)/TI-VAMP SNARE proteins. Here we studied whether Netrin-1-dependent neuronal migration relies on a similar SNARE mechanism. We show that migrating neurons in the lower rhombic lip (LRL) express several SNARE proteins, and that DCC co-associates with Sytx1 and TI-VAMP in these cells. We also demonstrate that cleavage of Sytx1 by botulinum toxin C1 (BoNT/C1) abolishes Netrin-1-dependent chemoattraction of migrating neurons, and that interference of Sytx1 functions with shRNAs or Sytx1-dominant negatives disrupts Netrin-1-dependent chemoattraction of LRL neurons. These findings indicate that a Sytx1/DCC interaction is required for Netrin-1 guidance of migrating neurons, thereby highlighting a relationship between guidance signaling and SNARE proteins that regulate membrane turnover.
authors.affiliation: Developmental Neurobiology and Regeneration Unit, Department of Cell Biology, Institute for Research in Biomedicine, Parc Cientific de Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), University of Barcelona, Barcelona, Spain.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cotrufo
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Andrés
authors.forename: Oriol
authors.initials: O
authors.lastname: Ros
authors.forename: Francesc
authors.initials: F
authors.lastname: Pérez-Brangulí
authors.forename: Ashraf
authors.initials: A
authors.lastname: Muhaisen
authors.forename: Giulia
authors.initials: G
authors.lastname: Fuschini
authors.forename: Ramón
authors.initials: R
authors.lastname: Martínez
authors.forename: Marta
authors.initials: M
authors.lastname: Pascual
authors.forename: Joan X
authors.initials: JX
authors.lastname: Comella
authors.forename: Eduardo
authors.initials: E
authors.lastname: Soriano
mesh_terms: D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D002531:Cerebellum / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects / Q000235:genetics; D000075389:DCC Receptor; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000075388:Netrin-1; D009474:Neurons / Q000378:metabolism*; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D050827:Syntaxin 1 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
chemical_list: D000075389:DCC Receptor; C501910:Dcc protein, mouse; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D050827:Syntaxin 1; D025521:Tumor Suppressor Proteins; D050988:Vesicle-Associated Membrane Protein 2; D000075388:Netrin-1; D001905:Botulinum Toxins