Translational Profiling Reveals Temporal Dynamics of Dendritic Protein Synthesis
Jones, Alexander.
2019
-
It is well
established that the long term storage of new memories requires on demand synthesis of
new proteins in the minutes and hours following that memories formation. This
requirement is specific to discrete subcellular compartments. Specifically, neuronal
dendrites synthesize new proteins locally and disruption of this process impairs
synaptic plasticity and long-term memory in hippocampal ... read moreslice experiments and in vivo
behavioral experiments, respectively. Although recent studies have attempted to
determine the translational profile of dendrites within the hippocampus, no current
consensus exists. Furthermore, it is not known how this translational profile changes
during the course of memory consolidation. Understanding the dynamics of protein
translation in dendrites is an important step in understanding why this process is
necessary for memory. Using a previously generated mouse line, which expresses an
EGFP-tagged ribosomal subunit under the control of the Camk2a promoter, we isolated
ribosome bound mRNA from dendrites and somata of projection neurons in CA1 of the
hippocampus. In a previous study we successfully used this technique combined with
RNAseq to generate a list of likely-dendritic mRNAs. Here we update this list,
considerably expanding the sample size used to generate our predictions. We find that
our updated list of dendritic predictions overlaps with some, though not all, of the
genes previously predicted to be dendritic. We compared mRNAs that are predicted to be
bound preferentially to ribosomes in dendrites versus in somata and found differences in
the untranslated regions of these genes underscoring the ability for elements of the
untranslated region to act as localization signals that target these genes to distinct
subcellular compartments. We further explored the translational profile of dendrites and
somata during the early time course after a behavioral learning paradigm. We find that
mRNAs in dendrites in particular experience an early and late phase of ribosome binding
increases as compared with mice that did not undergo a learning paradigm. These separate
phases of ribosome binding constitute a pool of mRNAs that are involved in functionally
distinct biological processes. Furthermore, the translational profiles of dendrites and
somata are almost entirely non-overlapping underscoring the point that changes in
protein synthesis during memory are subcellular compartment specific. The temporal
pattern of these phases of ribosome binding provides new insight into how local
translation within dendrites might be regulated in response to learning. We hope that in
addition, our results will be a resource to the field of local dendritic
translation.
Thesis (Ph.D.)--Tufts University, 2019.
Submitted to the Dept. of Neuroscience.
Advisor: Leon Reijmers.
Committee: Yongjie Yang, Rob Jackson, and Maribel Rios.
Keyword: Neurosciences.read less - ID:
- 8s45qn98w
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