Cited by 111Axon Guidance and Neuronal SignalingCellular transport and secretionNeurogenesis and neuroplasticity mechanisms

The TC10–Exo70 Complex Is Essential for Membrane Expansion and Axonal Specification in Developing Neurons

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Dupraz, Sebastián, Grassi, Diego, Bernis, María Eugenia, Sosa, Lucas, Bisbal, Mariano, Gastaldi, Laura, Jausoro, Ignacio, Cáceres, Alfredo +2 more·2009·The Journal of Neuroscience

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.

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Crossref · 10.1523/jneurosci.3907-09.2009

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  • The subcellular localization of the exocyst in these activated muscles is consistent with the known function of the exocyst in directing post-Golgi vesicles to target membranes for localized membrane addition.

    “The subcellular localization of the exocyst in these activated muscles is consistent with the known function of the exocyst in directing post-Golgi vesicles to target membranes for localized membrane addition”

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Authors
Dupraz, S., Grassi, D., Bernis, M. E., Sosa, L., Bisbal, M., Gastaldi, L., Jausoro, I., Cáceres, A., Pfenninger, K. H., & Quiroga, S.
Affiliations
  • Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
  • University of Colorado Anschutz (US)
Venue
The Journal of Neuroscience
Published
2009-10-21
Volume
29
Issue
42
Pages
13292-13301
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2031519211
Cited by
111
References
1
Citations by year
2026: 3 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 8 · 2020: 5 · 2019: 1 · 2018: 6 · 2017: 10 · 2016: 8 · 2015: 5 · 2014: 10 · 2013: 14 · 2012: 14
FWCI
3.92
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R01NS041029)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
TC10, Exo70, exocyst complex, axon elongation, neuronal polarity, IGF-1 signaling, PI3K signaling, growth cones, hippocampal pyramidal neurons
MeSH terms
Animals, Axons, Cells, Cultured, Chromones, Embryo, Mammalian, Enzyme Activation, Enzyme Inhibitors, Hippocampus, Insulin-Like Growth Factor I, Morpholines, Time Factors, Transfection, Receptor, IGF Type 1, Pyramidal Cells, rho GTP-Binding Proteins, Protein Transport, Cellular Structures, Vesicular Transport Proteins, RNA, Small Interfering, Green Fluorescent Proteins, Rats

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