Betydelsen av aminosyra transportörer i hjärnan för reglering av neurotransmittor nivåer
Tidsperiod: 2015-01-01 till 2015-12-31
Projektledare: Robert Fredriksson
Budget: 400 000 SEK
I have previously identified over 40 novel genes that code for new members of the solute carrier family and many of these are likely to be novel transporters for amino acids. A number of these were evolutionary related to glutamine transporters from the SLC38 family and glutamine transporters are known control the Glutamate/Glutamine/GABA cycle, a crucial system for neurotransmitter processing and regulation. We have data showing that two of these novel transporters are indeed glutamine transporters and their subcellular localization makes them the best candidates identified so far for being responsible for import of glutamine into neuronal synapses. We are using transgenic mice that we have generated, X. laevis oocyte expression, electrophysiology, Drosophila melanogaster genetics, primary neuronal cultures and advanced imaging techniques to firmly establish their function in neurotransmitter processing. We have also data showing that a novel transporter we found is a glutamate transporter expressed only on GABA neurons and could be a key molecule for signalling between inhibitory and excitatory neurons. We have generated conditional knockout mice to study the physiology of this transporter. We will continue to characterize other novel transporters from the same and related families regarding substrate profile and cellular localization. We will also study the evolution of the various families of amino acid transporters found in human to unravel their evolutionary origin.