Betydelsen av transportörer i nervsystemet i sjukdom och hälsa
Tidsperiod: 2017-01-01 till 2019-12-31
Budget: 2 100 000 SEK
This research plan describes a series of projects with an overall goal to elucidate how the amino acid transporters (SLCs) regulate neurotransmitter levels and energy metabolism in the brain.We usetransgenic mice and Drosophila melanogaster (fruit fly) as model systems combined with molecular biology and pharmacology to achieve this. We will investigate how novel glutamine transporters control the glutamate/glutamine/GABA (GGG) cycle, which is a key process regulating GABA and glutamate levels. We found that the most divergent member of the family, SLC38A10 (SNAT10), is expressed on Golgi of neurons. Our hypothesis is that SNAT10 is a sensor for amino acid availability, mediating this information through the mTORC1 pathway. Possibly SNAT10 is part of neuronal specific system regulating cell growth and metabolism, which could have implications for neuronal survival and neurodegenerative diseases. We have also developed a conditional knockout mouse line for another transporter, SLC18B1, and we have performed phenotypical characterization of this line. It is now clear that SLC18B1 encode a spermidine transporter and we have data showing it has a role in plasticity and memory. We will also investigate the global expression pattern of all SLCs in a neurons using single cell RNASeq to establish which transporters are frequently expressed together. This will be the first step to identify the combination of transporters that are responsible for a given physiological process.