The TC10–Exo70 Complex Is Essential for Membrane Expansion and Axonal Specification in Developing Neurons
| Autor: | Maria Eugenia Bernis, Lucas J. Sosa, Laura Gastaldi, Ignacio Jausoro, Mariano Bisbal, Karl H. Pfenninger, Alfredo Cáceres, Santiago Quiroga, Diego Grassi, Sebastian Dupraz |
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| Rok vydání: | 2009 |
| Předmět: |
rho GTP-Binding Proteins
Time Factors Neurite Morpholines Green Fluorescent Proteins Vesicular Transport Proteins Exocyst Biology Transfection Hippocampus Axonal growth cone Article Exocytosis Receptor IGF Type 1 medicine Animals Enzyme Inhibitors Insulin-Like Growth Factor I RNA Small Interfering Axon Growth cone Cells Cultured PI3K/AKT/mTOR pathway Pyramidal Cells General Neuroscience Embryo Mammalian Axons Cellular Structures Rats Cell biology Transport protein Enzyme Activation Protein Transport medicine.anatomical_structure nervous system Chromones |
| Zdroj: | The Journal of Neuroscience. 29:13292-13301 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.3907-09.2009 |
| Popis: | Axonal elongation is one of the hallmarks of neuronal polarization. This phenomenon requires axonal membrane growth by exocytosis of plasmalemmal precursor vesicles (PPVs) at the nerve growth cone, a process regulated by IGF-1 activation of the PI3K (phosphatidylinositol-3 kinase) pathway. Few details are known, however, about the targeting mechanisms for PPVs. Here, we show, in cultured hippocampal pyramidal neurons and growth cones isolated from fetal rat brain, that IGF-1 activates the GTP-binding protein TC10, which triggers translocation to the plasma membrane of the exocyst component exo70 in the distal axon and growth cone. We also show that TC10 and exo70 function are necessary for addition of new membrane and, thus, axon elongation stimulated by IGF-1. Moreover, expression silencing of either TC10 or exo70 inhibit the establishment of neuronal polarity by hindering the insertion of IGF-1 receptor in one of the undifferentiated neurites. We conclude that, in hippocampal pyramidal neurons in culture, (1) membrane expansion at the axonal growth cone is regulated by IGF-1 via a cascade involving TC10 and the exocyst complex, (2) TC10 and exo70 are essential for the polarized externalization of IGF-1 receptor, and (3) this process is necessary for axon specification. |
| Databáze: | OpenAIRE |
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