RT Journal Article
SR Electronic
T1 The TC10–Exo70 Complex Is Essential for Membrane Expansion and Axonal Specification in Developing Neurons
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 13292
OP 13301
DO 10.1523/JNEUROSCI.3907-09.2009
VO 29
IS 42
A1 Sebastián Dupraz
A1 Diego Grassi
A1 María Eugenia Bernis
A1 Lucas Sosa
A1 Mariano Bisbal
A1 Laura Gastaldi
A1 Ignacio Jausoro
A1 Alfredo Cáceres
A1 Karl H. Pfenninger
A1 Santiago Quiroga
YR 2009
UL http://www.jneurosci.org/content/29/42/13292.abstract
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.