Biology Reference
In-Depth Information
synapse. Work from Schratt and colleagues identified a number of miRNAs
enriched in synaptosomes prepared from hippocampal neurons in culture.
Among these, mir-218 and mir-138 were the most significant (
Siegel
et al
.,
2009
). The authors further showed that mir-138 is a negative regulator of
dendritic spine size, acting through the local repression of the synthesis of
the depalmitoylation enzyme Lypla1/APT1 which, in turn, affects the
membrane localization of a G protein involved in Rho signaling and
actomyosin contraction. Finally, Kaplan and colleagues characterized the
pool of miRNAs present in distal axons and compared them to those in the
soma of sympathetic neurons in culture (
Natera-Naranjo
et al
., 2010
).
Kaplan and colleagues had previously shown that mir-338, which was not
detected as being significantly enriched in axons in their later work, is
present in axons as shown by
in situ
hybridization and is able to regulate
cytochrome
c
oxidase IV, ATP levels, and thus the rate of neurotransmitter
uptake in axons (
Aschrafi
et al
., 2008
). Therefore, even those miRNAs
which are not significantly enriched in these compartments can potentially
have localized roles, for example, if their targets are spatially restricted.
While there is little overlap between the miRNAs identified in all these
different studies, which could be due to the differences in samples and
methodologies, these will likely prove to be useful resources for further
studies. In addition, some conclusions are shared by different studies. For
example, mir-124, one of the most abundant neuronal miRNAs, has been
shown by two of these studies to be enriched in the soma (this is in contrast
to mir-124 in
Aplysia
where it has been seen in the projections of sensory
neurons), suggesting some kind of exclusion mechanism from the processes.
Having miRNA-mediated regulation in the synaptic terminals in addi-
tion to the regulation in the soma has two obvious advantages. First, a
miRNA present both in the processes and in the soma can cause two types
of effects as illustrated by mir-134 and mir-132, a rapid, localized one at the
former (typically by targeting synaptic proteins), and perhaps a slower, more
sustained one at the latter (typically by targeting transcriptional or posttran-
scriptional regulators). And second, it can allow for uncoupled global and
local responses carried out by the same miRNA, as discussed for mir-134 in
Section 2.1.4
. Further characterization of how miRNAs are transported
through the different compartments and how this transport is regulated will
be critical to our understanding of how miRNAs contribute to neuronal
development and function.
3.2. Activity-dependent regulation of miRNA
biogenesis and activity
Neuronal activity is an important player during the maturation phase of
neuronal development, as it modulates the establishment and refinement of
neuronal connections, mainly through its effects on dendrite morphology
