Dynamics of local protein synthesis in cortical neuronal dendrites and their regulation: Examining the effects of 3’UTRs in mRNA localisation and translation
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2023-03-07
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en
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Abstract
Neurons adjust the types and levels of proteins they produce in response to changes in
synaptic transmission. It was initially believed that protein translation was confined to the
somatic space. However, ample evidence has shown that these processes occur in localised,
remote regions far from the central nucleus1. This ability to autonomously adapt the local
proteome – which refers to all the proteins a cell produces – allows neurons to respond
dynamically to changes in their environment2. The need for local and independent protein
synthesis in distal dendrites is crucial for synaptic plasticity to occur3,4, as it allows for quick
responses to changes in neural activity. It also enables neurons to overcome the logistical
challenges associated with rapidly transporting new proteins from the soma to distal sites5.
Understanding how neurons regulate the production of different proteins is crucial to
appreciate how the brain processes information and adapts to new situations. Gaining a
deeper insight into the mechanisms that govern protein synthesis could have far-reaching
implications for treating neurological disorders related to imbalances in protein synthesis,
degradation, and disruptions in synaptic function. Examples of such diseases include Autism
Spectrum Disorders, Fragile X Syndrome, and Alzheimer's disease6,7. It has been shown that
the localisation motifs required for transporting mRNAs are found in the 3’ untranslated
region (UTR)8–12. Therefore, a valuable way to visualise local protein synthesis has been to
design and implement fluorescent reporters containing 5’ and 3’ UTRs of candidate
mRNAs13,14.
Although there is an abundance of research on the translation of mRNAs and local synthesis
of proteins at the synapse, the dynamic visualisation of local protein synthesis in vivo during
learning and memory has yet to be realised. Currently, Dr. Donlin-Asp and Teresa Spanò in
the Schuman lab are addressing this question by using fluorescent reporters with UTRs from
Beta Actin and Psd95 to visually analyse local protein synthesis dynamics and regulation in
vivo. To ensure that these reporters are robust tools to measure local translation, this thesis
project aims to visualise the spatial distribution and expression of these mRNA reporters
compared to their endogenous correlates.
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Faculteit der Sociale Wetenschappen