| Title | The TC10-Exo70 complex is essential for membrane expansion and axonal specification in developing neurons. | | Author(s) | Dupraz S, Grassi D, Bernis ME, Sosa L, Bisbal M, Gastaldi L, Jausoro I, Cáceres A, Pfenninger KH, Quiroga S | | Institution | Departamento de Química Biológica y Centro de Investigaciones en Química Biológica de Córdoba, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba-Consejo Nacional de Investigaciones Científicas y Técnicas, 5000 Córdoba, Argentina. | | Source | J Neurosci 2009 Oct 21; 29(42):13292-301. | | MeSH | Animals
Axons
Cells, Cultured
Cellular Structures
Chromones
Embryo, Mammalian
Enzyme Activation
Enzyme Inhibitors
Green Fluorescent Proteins
Hippocampus
Insulin-Like Growth Factor I
Morpholines
Protein Transport
Pyramidal Cells
RNA, Small Interfering
Rats
Receptor, IGF Type 1
Time Factors
Transfection
Vesicular Transport Proteins
rho GTP-Binding Proteins
| | Abstract | 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. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
| | PubMed ID | 19846717 |
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