title: The Motor KIF5C Links the Requirements of Stable Microtubules and IGF-1 Receptor Membrane Insertion for Neuronal Polarization.
abstract: Three early signals of asymmetry have been described to occur in a single neurite of neurons at stage 2 of differentiation (before polarization) and shown to be essential for neuronal polarization: (i) accumulation of stable microtubules, (ii) enrichment of the plasma membrane with activatable IGF-1r, and (iii) polarized transport of the microtubular motor KIF5C. Here, we studied the possible relationship between these three phenomena. Our results show that the activatable (membrane-inserted) IGF-1r and stable microtubules accumulate in the same neurite of cells at stage 2. The polarized insertion of IGF-1r depends on microtubule dynamics as shown using drugs which modify microtubule stability. Silencing of KIF5C expression prevents the polarized insertion of IGF-1r into the neuronal plasmalemma and neuronal polarization. Syntaxin 6 and VAMP4, necessary for the polarized insertion of the IGF-1r, are associated to vesicles carried by the microtubular motor KIF5C and is transported preferentially to the neurite where KIF5C accumulates. We conclude that the enrichment of stable microtubules in the future axon enhances KIF5C-mediated vesicular transport of syntaxin 6 and VAMP4, which in turn mediates the polarized insertion of IGF-1r in the plasmalemma, a key step for neuronal polarization. We herewith establish a mechanistic link between three early polarity events necessary for the establishment of neuronal polarity.
authors.affiliation: Departamento de Química Biológica-CIQUIBIC, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba-CONICET, Haya de la Torre esquina Medina Allende, Ciudad Universitaria, 5000, Córdoba, Argentina.
authors.forename: Mariana
authors.initials: M
authors.lastname: Oksdath
authors.affiliation: Departamento de Química Biológica-CIQUIBIC, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba-CONICET, Haya de la Torre esquina Medina Allende, Ciudad Universitaria, 5000, Córdoba, Argentina.
authors.forename: Alvaro F Nieto
authors.initials: AFN
authors.lastname: Guil
authors.affiliation: Departamento de Química Biológica-CIQUIBIC, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba-CONICET, Haya de la Torre esquina Medina Allende, Ciudad Universitaria, 5000, Córdoba, Argentina.
authors.forename: Diego
authors.initials: D
authors.lastname: Grassi
authors.affiliation: Departamento de Química Biológica-CIQUIBIC, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba-CONICET, Haya de la Torre esquina Medina Allende, Ciudad Universitaria, 5000, Córdoba, Argentina.
authors.forename: Lucas J
authors.initials: LJ
authors.lastname: Sosa
authors.affiliation: Departamento de Química Biológica-CIQUIBIC, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba-CONICET, Haya de la Torre esquina Medina Allende, Ciudad Universitaria, 5000, Córdoba, Argentina. squiroga@fcq.unc.edu.ar.
authors.forename: Santiago
authors.identifier: http://orcid.org/0000-0001-9087-7591
authors.initials: S
authors.lastname: Quiroga
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D050765:Qa-SNARE Proteins / Q000378:metabolism; D050683:R-SNARE Proteins / Q000378:metabolism; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D050257:Tubulin Modulators; C533192:VAMP4 protein, rat; D015638:Cytochalasin D; D017526:Receptor, IGF Type 1; C000612996:KIF5C protein, rat; D016547:Kinesins; D017239:Paclitaxel; D015739:Nocodazole
keywords: IGF-1 receptor; KIF5C; Neuronal differentiation; Neuronal polarization; Stable microtubules; Syntaxin 6