Actin Isoforms in Neuronal Development and Function - International Review of Cell and Molecular Biology - page 176

accumulating on the side of the growth cone opposite to the gradient. And
finally, treatment with antisense oligonucleotides to the β-actin zipcode
sequence blocked attractive but also repulsive growth cone turning, which
was in contrast to what was observed in the first report.
Collectively, these two prominent studies demonstrated that β-actin
mRNA and protein accumulate asymmetrically on the side of the growth
cone adjacent to an attractive guidance cue gradient, and that blocking
this by either perturbing the interaction of β-actin mRNA with ZBP3 or
blocking β-actin synthesis significantly decreased the ability of the growth
cone to turn toward attractive guidance cues (and in one of the studies away
from repulsive ones) ( Leung et al., 2006 ; Yao et al., 2006 ). The strong data
from these reports thus suggest that the localization and local translation of
β-actin is a critical mechanism for mediating the localized accumulation of
actin required for growth cone turning.
It remains controversial how well the local translation of β-actin is
conserved in higher vertebrates, with data from some studies supporting
its conservation while others have refuted it. Recent work characterizing
cortical neurons cultured from ZBP1 KO mice demonstrated that ZBP1 is
indeed required for attractive growth cone turning to netrin-1 and BDNF.
However, β-actin protein accumulation in growth cones stimulated with
BDNF was only very subtly decreased in the absence of ZBP1 ( Welshhans
and Bassell, 2011 ). This might suggest that other ZBP family members
such as ZBP2 and 3 are able to compensate for the loss of ZBP1. Alterna-
tively, the mislocalization of other RNAs localized by ZBP1 and critical
for growth cone turning may be more severely affected than β-actin, the
only RNA examined. As a more direct test of a role for the local translation
of β-actin within mammalian axons, Vogelaar et al. cultured perinatal rat
dorsal root ganglion (DRG) in compartmented chambers allowing for the
specific manipulation of axons without affecting the neuronal cell bodies
in a separate chamber. Treatment of axons with siRNAs against β-actin
significantly reduced β-actin mRNA levels within axons, but not within
the isolated neuronal cell bodies. Following axonal transection, control
axons underwent a brief period of retraction followed by the reformation
of a growth cone, while axons treated with the siRNA targeted against
β-actin failed to reform a growth cone ( Vogelaar et al., 2009 ). We recently
demonstrated that β-actin-deficient motor axons functionally regenerate
after peripheral nerve injury, however, suggesting that at least some axons
are capable of regenerating in vivo in the complete absence of β-actin
( Cheever et al., 2011 ).