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Tue, 11 Mar 2025 11:30 AM ASB 10900, Big Data Hub

How purinergic neurotransmission is still rosé when ATP transporters can't find the right APT

ATP is best known as the energy currency of our cells, but it is also a diverse intracellular signalling molecule and neurotransmitter that is "co-released" with norepinephrine from sympathetic nerves. These sympathetic nerves are essential for controlling the contractile tone of blood vessels, and thus regional blood flow and blood pressure. However, at the molecular lever, we really don’t understand how these nerves package and release two neurotransmitters. Discovery of the Vesicular Nucleotide Transmitter as the likely pump that loads ATP into vesicles open the door to studying ATP release using molecular tools. We have studied the sympathetic nerves of rait tail arteries and cultured cells to understand how ATP is packaged into vesicles and released as a neurotransmitter. Through immuno-staining, studying GPF-tagged versions of VNUT, pH-sensitive versions of VNUT and using bioinformatics and machine learning to guide the creation of VNUT chimeras, we have found that VNUT is unique among a large family of neurotransmitter transporters in that it does not localize to traditional vesicles. I will explain why we think that VNUT might unusually contribute to the maintenance of releasable ATP stores from a sub-cellular 'APT' upstream of vesicles to keep purinergic signalling all rosé.