UBC Theses and Dissertations
Roles of Basigin in structure and function of the Drosophila peripheral nerve Hunter, Amelia Catherine
The peripheral nervous system is made up of the nerves which extend out of the central nervous system and carry signals to and from different body regions. The structure and function of the peripheral nerves is dependent upon the molecular composition of the neurons and glial cells that form the nerve. In Drosophila, the protein-protein interactions that facilitate proper neurotransmission and uphold the structural integrity of the nerve have not been fully characterized. This thesis describes a conserved transmembrane protein, Basigin, and its role in interacting with different proteins in the neurons and glia to maintain nerve structure and function. The peripheral nerves are ensheathed in different layers of glia and extracellular matrix. The perineurial glia (the outermost glial layer) express Basigin, and we have shown that knockdown of Basigin expression in these cells causes an inward constriction of the glia and the overlying extracellular matrix. This constriction results in a disruption of the septate junction morphology and breakage of the glial cytoskeleton. Reduction of the level of integrin, one of the binding partners of Basigin, rescues this phenotype indicating that the absence of Basigin causes dysregulation of the integrin-based focal adhesions. Basigin is also expressed at high levels in the axons of the nerve roots exiting the central nervous system. The transition zone between the central and peripheral nervous system has previously been identified as a site of initiation for the motor neuron action potential. We found that this region is enriched in two markers of the axon initial segment, scaffolding protein Ankyrin-1 and the voltage-gated potassium channel Shal. Basigin also co-localizes with another scaffolding protein, Discs large 1, and the calcium ion pump PMCA. PMCA also cannot localize to this region in the absence of Basigin expression. We propose that this transition zone is the location of the axon initial segment where the motor nerve impulses are generated. Overall, these results show that Basigin’s protein-protein interactions in the neurons and glia of the peripheral nerves help to uphold the structure and function of the nerve.
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