QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 21, 2009, 29(42):13292-13301; doi:10.1523/JNEUROSCI.3907-09.2009

This Article Full Text Full Text (PDF) Supplemental Material Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Dupraz, S. Articles by Quiroga, S. PubMed PubMed Citation Articles by Dupraz, S. Articles by Quiroga, S.

 Previous Article  |  Next Article 

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

Sebastián Dupraz,¹ Diego Grassi,¹ María Eugenia Bernis,¹ Lucas Sosa,^1,3 Mariano Bisbal,² Laura Gastaldi,² Ignacio Jausoro,² Alfredo Cáceres,² Karl H. Pfenninger,³ and Santiago Quiroga¹

¹Departamento 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 (CONICET), 5000 Córdoba, Argentina, ²Instituto de Investigación Médica Mercedes y Martín Ferreyra–CONICET, 5016 Córdoba, Argentina, and ³Colorado Intellectual and Developmental Disabilities Research Center and Department of Pediatrics, University of Colorado Denver, Aurora, Colorado 80045

Correspondence should be addressed to Santiago Quiroga, Departamento de Química Biológica–Centro de Investigaciones en Química Biológica de Córdoba, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba–Consejo Nacional de Investigaciones Científicas y Técnicas, Haya de la Torre esquina Medina Allende, Ciudad Universitaria, 5000 Córdoba, Argentina. Email: squiroga{at}mail.fcq.unc.edu.ar

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.

---

Received Aug. 10, 2009; accepted Sept. 3, 2009.

Correspondence should be addressed to Santiago Quiroga, Departamento de Química Biológica–Centro de Investigaciones en Química Biológica de Córdoba, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba–Consejo Nacional de Investigaciones Científicas y Técnicas, Haya de la Torre esquina Medina Allende, Ciudad Universitaria, 5000 Córdoba, Argentina. Email: squiroga{at}mail.fcq.unc.edu.ar

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help