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and spine enlargement during synaptic plasticity in rat hippocampal neurons
by relieving miR-134 inhibition of LIMK1 translation, suggesting neuro-
trophin signaling can regulate the postsynaptic proteome during long-term
potentiation in mature neurons (
Schratt et al., 2006
). Second, miR-134 is
also enriched in cultured
Xenopus
spinal neuron growth cones where LIMK
RNA is also an miR-134 target. Overexpressing miR-134 mimics or anti-
sense inhibitors blocked protein synthesis-dependent turning responses to a
BDNF gradient but not protein synthesis-independent turning responses to
BMP-7 (
Han et al., 2011
), showing that BDNF signaling may also regulate
protein synthesis in the growth cone by relieving miRNA inhibition to ef-
fect growth cone guidance. A challenge for future studies will be determin-
ing how and whether local signaling endosome signaling regulates the local
translation of proteins that operate in the growth cone generally and whether
these mechanisms operate
in vivo
.
3. SIGNALING ENDOSOME SIGNALING IN THE
GROWTH CONE
Howdo signaling endosomes act locally to steer growth cones? Turning
a growth cone requires the coordinated polarization of at least three distinct
but interrelated events: membrane exo- and endocytosis, cytoskeletal assem-
bly and disassembly, and substrate adhesion formation and turnover. Mount-
ing evidence from various systems suggests that each of these events can be
directly impacted by neurotrophin signaling endosome signaling.
3.1. Exo- and endocytosis
How do neurotrophin signaling endosomes influence exo- and endocytosis
to steer growth cones?
Extracellular gradients of secreted proteins including neurotrophins direct
neuronalmigration (
Song&Poo, 2001
) andpolarization (
Arimura&Kaibuchi,
2007
), and growth cone guidance (
Dickson, 2002; Tessier-Lavigne &
Goodman, 1996
)
in vitro
and
in vivo
by directing the polarized addition and
subtraction of plasma membrane via selective exo- and endocytosis (
Itofusa
&Kamiguchi,2011
). In response to both attractive and repulsive cues,
growth cones turn away from exocytosis and toward endocytosis and the
balance between the two determines the direction of growth (
Hines, Abu-
Rub, & Henley, 2010; Kolpak et al., 2009; Tojima et al., 2007; Tojima,
Itofusa, & Kamiguchi, 2010
). Polarized exo- and endocytosis may be
