PT  - JOURNAL ARTICLE
AU  - Sebastián Dupraz
AU  - Diego Grassi
AU  - María Eugenia Bernis
AU  - Lucas Sosa
AU  - Mariano Bisbal
AU  - Laura Gastaldi
AU  - Ignacio Jausoro
AU  - Alfredo Cáceres
AU  - Karl H. Pfenninger
AU  - Santiago Quiroga
TI  - The TC10–Exo70 Complex Is Essential for Membrane Expansion and Axonal Specification in Developing Neurons
AID  - 10.1523/JNEUROSCI.3907-09.2009
DP  - 2009 Oct 21
TA  - The Journal of Neuroscience
PG  - 13292--13301
VI  - 29
IP  - 42
4099  - http://www.jneurosci.org/content/29/42/13292.short
4100  - http://www.jneurosci.org/content/29/42/13292.full
SO  - J. Neurosci.2009 Oct 21; 29
AB  - 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.