Actin Isoforms in Neuronal Development and Function - International Review of Cell and Molecular Biology - page 177

Even more data contesting the relevance of local β-actin translation
in growth cone guidance surfaced when it was demonstrated that local
protein synthesis in total within axons was not required for growth cone
turning responses to a variety of attractive and repulsive cues including
ephrin-A2, slit-3, sema3A, NGF, and neurotrophin-3 (NT-3) ( Roche et al.,
2009 ). In contrast to the previous studies restricted to the Xenopus system,
multiple neuronal subtypes and species were tested including chick retinal,
sympathetic, DRG and mouse DRG neurons. This group showed that
treatment with attractive guidance cues did induce a significant increase
in the amount of F-actin within the growth cone by phalloidin staining,
but that this was not dependent on protein synthesis and not due to an
increase in β-actin protein levels based on immunofluorescence. Instead,
β-actin was redistributed to the peripheral domain suggesting that the
β-actin protein already present is sufficient for guided growth cone motil-
ity. RhoA, another protein previously reported to be locally translated
within growth cones in response to guidance cues, was also not found
to be locally translated in this study as well, further confirming that local
translation within axons is not required for turning responses at least in the
neuronal types examined.
One intriguing explanation offered by this group as to why their
results differed from what has been reported by others is that the energy
and metabolic demands of the various types of neurons examined across
different species may differ. Based upon the estimated number of ribo-
somes within a growth cone, the translation rate of an actin monomer,
and the magnitude of the increased β-actin synthesis observed in response
to netrin-1, Xenopus growth cones would likely contain 100 times less
β-actin than chick DRG growth cones for example ( Roche et al., 2009 ).
Dramatically different levels of β- and γ-actin in Xenopus spinal neurons
as compared to chick DRG neurons was later directly demonstrated with
multiple antibodies including some validated on β- and γ-actin KO tissue
( Marsick et al., 2010 ). Additionally, Xenopus neurons were found to have a
decreased F-:G-actin ratio compared to chick DRG neurons, which could
have significant effects on actin dynamics and possibly even gene expres-
sion ( Marsick et al., 2010 ). Thus, these studies raise the possibility that the
local translation of β-actin may be essential for proper growth cone turn-
ing in Xenopus neurons, which express actin at much lower levels than in
higher vertebrate growth cones where the local synthesis of β-actin does
not appear to be required.