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In-Depth Information
filopodial targeting of the sec6/8 exocyst complex (
Hazuka et al., 1999
).
While direct links between the regulation of endo/exocytosis and filopodial
dynamics during growth cone guidance remain to be fully elucidated, it
promises to be venue worth exploring. These studies emphasize that mem-
brane turnover in filopodia is of functional significance during the early
presynaptic stages of axon development.
3.4. Localized Protein Synthesis and Regulation of Filopodia
Neuronal synapses are highly localized subcellular structures that can oper-
ate independently of one another. Thus, the neuron must be able to control
its physiology with a high degree of subcellular specificity. In contrast, while
dendrites can be a few hundred micrometers in length, axons can be over
a meter long. Thus, the neuron must also have mechanism that allows it to
provide these processes, a long ways away from the cell body, with all the
required cellular components (e.g. proteins and organelles). This require-
ment is met, at least in part, by axonal transport which delivers cargoes gen-
erated within the cell body to distal dendrites and axons. However, neurons
also have the ability to locally synthesize proteins, both within dendrites and
axons (
Yoo et al., 2010
;
Jung et al., 2012
). This endows neurons with the
ability to locally regulate their proteome, a property termed
merotrophism
(
Court and Alvarez, 2005
). In addition, localized protein degradation also
acts in concert with protein synthesis to control the local proteome (
Twiss
and van Minnen, 2006
). Genome-wide screens of the mRNA content of
developing and adult sensory axons identified over 1000 mRNA species
(
Gumy et al., 2011
). mRNAs encoding cytoskeletal and cytoskeletal regula-
tory proteins are found in axons. Localized protein synthesis is required for
alterations in synaptic function during learning and memory (
Bramham,
2008
), and also during the guidance of axons to their targets (
Donnelly
et al., 2010
). This section reviews recent evidence that localized protein
synthesis contributes to the formation and dynamics of neuronal filopodia.
β-actin was the first protein shown to undergo localized synthesis in the
growth cones of developing axons (
Zhang et al., 2001
). While the mecha-
nistic role of locally synthesized β-actin remains unclear (i.e. why does the
neuron need to locally synthesize β-actin when at any time, only approxi-
mately 50% of it is in filamentous form), it is required for growth cone
turning toward attractant signals (
Jung et al., 2012
). mRNAs are targeted
into axons and dendrites through the association with ribonucleic protein
particles (RNPs), which undergo transport and also regulate the availabil-
ity of mRNAs for translation into protein. mRNAs associate with RNPs
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