Research article summary (published 19 Oct 2009):

The TC10-Exo70 complex is essential for membrane expansion and axonal specification in developing neurons.

Full 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.

Author information

Author/s: Dupraz, Sebastián (S); Grassi, Diego (D); Bernis, María Eugenia (ME); Sosa, Lucas (L); Bisbal, Mariano (M); Gastaldi, Laura (L); Jausoro, Ignacio (I); Cáceres, Alfredo (A); Pfenninger, Karl H (KH); Quiroga, Santiago (S);

Affiliation: 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.

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2009-Oct; vol 29 (issue 42) : pp 13292-301

Dates: Created 2009/10/22; Completed 2009/11/06;

PMID: 19846717, status: MEDLINE (last retrieval date: 11/6/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Axons - drug effects; physiology; ultrastructure Cells, Cultured Cellular Structures - drug effects; metabolism Chromones - pharmacology Embryo, Mammalian Enzyme Activation - drug effects Enzyme Inhibitors - pharmacology Green Fluorescent Proteins - genetics Hippocampus - cytology Insulin-Like Growth Factor I - pharmacology

Insulin-Like Growth Factor I - pharmacology Morpholines - pharmacology Protein Transport - drug effects; physiology Pyramidal Cells - cytology RNA, Small Interfering - genetics; metabolism Rats Receptor, IGF Type 1 - physiology Time Factors Transfection - methods Vesicular Transport Proteins - metabolism rho GTP-Binding Proteins - metabolism

Associated Chemicals: Chromones (0) ; Enzyme Inhibitors (0) ; Exoc7 protein, rat (0) ; Morpholines (0) ; RNA, Small Interfering (0) ; Vesicular Transport Proteins (0) ; Green Fluorescent Proteins (147336-22-9) ; 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (154447-36-6) ; Insulin-Like Growth Factor I (67763-96-6) ; Receptor, IGF Type 1 (EC 2.7.1.112) ; Rhoq protein, rat (EC 3.6.1.-) ; rho GTP-Binding Proteins (EC 3.6.5.2)

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