Actin Isoforms in Neuronal Development and Function - International Review of Cell and Molecular Biology - page 180

required for growth cone guidance, we would have expected to see a similar
defect in the rostral corpus callosum, which crosses the midline at approxi-
mately the same time ( Richards et al., 2004 ).
In summary, strong data from cultured Xenopus neuron systems indicat-
ing that the asymmetric local translation of β-actin is required for growth
cone guidance have not been definitively confirmed in higher vertebrate
cell culture or in vivo models. This is significant because β-actin is the most
commonly cited and utilized reporter for local translation in growth cones,
as well as one of the most commonly cited paradigms for the functional
relevance of local translation. ZBP1 appears to be required for growth cone
guidance in mammalian neurons in vitro, however, and so it remains pos-
sible that the localization and local translation of any of the other several
hundred transcripts shown to interact with ZBP1 could be contributing to
growth cone guidance while the association with β-actin could simply be
due to a nonfunctional bystander effect. Caution should thus be employed
when extrapolating function to the localization of β-actin mRNA and pro-
tein at least within growth cones of higher vertebrates at this time.
5.2.2. Local Translation of β -Actin in Dendrites and Dendritic Spine
Morphogenesis
Local translation within developing and mature dendrites is generally
more widely accepted than local protein synthesis in growth cones due to
the prohibitively large distances proteins would need to be transported in
mature neurons versus the relatively shorter distances in developing neurons
( Bramham, 2008 ; Job and Eberwine, 2001 ; Sutton and Schuman, 2006 ).
Furthermore, a large number of these studies have implicated local pro-
tein synthesis as a critical factor modulating synaptic plasticity. Although
ZBP1 levels decrease substantially with age in mice ( Nielsen et al., 1999 ;
Runge et al., 2000 ), a small number of studies have now identified endog-
enous ZBP1 expression in the dendrites of mature cultured neurons ( Eom
et al., 2003 ; Perycz et al., 2011 ; Tiruchinapalli et al., 2003 ), raising the pos-
sibility that the regulated local translation of β-actin could play a role in
dendrite development or synaptic plasticity. These few studies have likely
just scratched the surface of potential actin isoform functions in dendrites,
however, and given the significant memory and behavioral defects identi-
fied in CNS- Actb KO mice, we feel this area is among the most promising
and exciting that remains to be explored in actin isoform neurobiology.
One recent study examined the role of ZBP1 and β-actin localization
in regulating the dendritic morphology of cultured hippocampal neurons.