The presynaptic protein Mover is heterogeneously expressed across brain areas and synapse types
by Rebecca Wallrafen
Date of Examination:2019-02-18
Date of issue:2019-06-24
Advisor:Prof. Dr. Thomas Dresbach
Referee:Prof. Dr. Thomas Dresbach
Referee:Prof. Dr. Nils Brose
Persistent Address:
http://dx.doi.org/10.53846/goediss-7523
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Abstract
English
Synaptic nerve terminals are highly specialized sites where complex processes are taking place. The regulation of these complex processes is mediated by an intricate machinery of presynaptic proteins. While most of these proteins are evolutionarily conserved, a remarkably small number occurs only in vertebrates. They may increase the complexity and convey specialization to vertebrate synapses, thereby potentially bridging the gap between simple and complex behaviors. Among the vertebrate-specific proteins are the scaffolding molecules Bassoon and Piccolo, the synaptic vesicle associated protein Synuclein and Mover. Mover is a small, synaptic vesicle attached phosphoprotein that was first discovered as a binding partner of the scaffolding molecule Bassoon. Its expression is regulated by activity. While most of its function remains unknown, knockout experiments showed that Mover buffers synaptic plasticity at the mossy fiber synapse in the hippocampus. Knockdown of Mover at the calyx of Held increased synaptic release probability and accelerated synaptic vesicle reloading. Already in the first publication Mover was described to be heterogeneously expressed, and was found at subsets of synapses, while it seemed absent from others. In this study I have first established a quantitative immunofluorescence approach, comparing Mover fluorescence intensity to that of an internal reference marker, i.e. Synaptophysin, to determine the relative Mover abundance. I find that Mover is heterogeneously expressed, with high levels in some brain regions, such as the ventral pallidum, septal nuclei and the amygdala, and low levels relative to Synaptophysin in other brain regions, such as the primary motor cortex and the granular layer of the cerebellum. I also applied the quantification approach to the different layers of the hippocampus and find that Mover is enriched in layers that are associated with intra-hippocampal computation, and that Mover levels are low in input- and output layers. Next, I characterized Mover at the endbulb of Held, i.e. first relay station of the binaural pathway which is responsible for hearing. I find that while absolute Mover levels are higher at inhibitory synapses contacting bushy cells than at endbulbs, the amount of Mover per synaptic vesicle is higher at endbulbs. Together, the data confirm the heterogeneous distribution of Mover on three distinct levels: (1) across brain regions; (2) within single brain regions; (3) across synapse types. Its differential association with synapses on the level of brain areas, subregions and types of synapses renders Mover a candidate for a protein that generates synaptic heterogeneity.
Keywords: Synapse; Mover; Distribution
