The role of ABCC5 in the transport of inhibitory neuropeptides into vesicles
<p>ABCC5 is an ATPase dependent membrane transporter capable of transporting many structurally unrelated substrates such as glutamate conjugates and cyclic nucleotides. Previous work has found that high ABCC5 expression in human adipose tissue has been associated with an increased incidence of...
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| Format: | Thesis |
| Language: | English |
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2020
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| Summary: | <p>ABCC5 is an ATPase dependent membrane transporter capable of transporting many structurally unrelated substrates such as glutamate conjugates and cyclic nucleotides. Previous work has found that high ABCC5 expression in human adipose tissue has been associated with an increased incidence of Type 2 diabetes mellitus. Global Abcc5 knock-out mice had significant accumulation of the inhibitory neuropeptide N-acetylaspartylglutamate in their brains and had reduced adipose tissue depots, were more insulin sensitive and had raised post-prandial plasma levels of the incretin hormone GLP-1. We propose that ABCC5 may be involved with the loading of NAAG into synaptic-like microvesicles in gut endocrine cells and neurons. The work outlined here aimed to identify where ABCC5 is expressed in gut endocrine cells and to confirm the NAAG transporter activity of ABCC5. Through fixed cell immunolabelling and live cell dye staining, we show that ABCC5 is not expressed on the cell membrane of model enteroendocrine cells and has a punctate, intracellular expression pattern. We also adapted a method to isolate ex vivo synaptic vesicles from mouse brains and developed a vesicular transport assay with NAAG13C5 substrate detection based on NMR spectroscopy. The preliminary data we have generated supports our hypothesis that ABCC5 is expressed intracellularly and participates in the loading of substrates in intracellular vesicle pools.</p> |
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