Actin Isoforms in Neuronal Development and Function - International Review of Cell and Molecular Biology - page 173

was found within the axonal tracts of the cerebellar white matter while
β-actin staining was virtually nonexistent ( Fig. 4.2 , arrows). Staining of axo-
nal tracts within the striatum revealed this same pattern, again with γ-actin
present while β-actin was noticeably absent ( Fig. 4.2 , arrows). The lack of
β-actin staining observed in large axonal bundles from adult animals is in
agreement with the previous studies described above ( Weinberger et al.,
1996 ), providing further support that β-actin is either absent or at rela-
tively low levels compared to γ-actin in large axonal bundles. However,
this was the only case of distinct localization between β- and γ-actin that
we observed, suggesting that β- and γ-actin may be colocalized to a much
greater degree than previously thought within both individual neurons
and distinct brain regions. We only used antibodies and staining conditions
which were verified on KO tissue, which may explain some of the localiza-
tion differences we observed compared to previous studies.
5.2. Roles for the Localization and Local Translation of β -Actin
As discussed in Section 3.2 , the localization and local translation of β-actin
is one of the, if not the most, studied aspect of actin isoform biology. This
is also true in neurons, where there is significant evidence for critical func-
tions of the local translation of specifically β-actin in neuronal development,
function, disease, and regeneration. It is worth noting, however, that the
primary aim of these studies was to characterize and elucidate mechanisms
mediating mRNA localization and local translation in general, while β-actin
was most often used simply as a reporter for this process. In this section, we
will focus our discussion on the evidence most directly relevant to specific
actin isoform functions in neurons. The reader is also referred to excellent
reviews elsewhere ( Jung et al., 2012 ; Swanger and Bassell, 2011 ) for more
in-depth discussions on the broader mechanisms of mRNA localization
and local translation in developing neurons.
5.2.1. Local β -Actin Translation in Growth Cone Guidance
Following differentiation and migration, neurons in the developing CNS
send out axons in search of specific synaptic targets. The task of ensuring
the proper wiring of the nervous system falls to the axonal growth cone,
which must interpret multiple soluble and cell-bound guidance cues to
traverse sometimes vast distances in the developing CNS ( Lowery and Van
Vactor, 2009 ; Tessier-Lavigne and Goodman, 1996 ). The actin cytoskeleton
is enriched in the peripheral domain of the growth cone, where localized
asymmetric polymerization can initiate guided growth cone protrusion and
turning. Given that the ultimate function of guidance cues is to provide