Amino acid exchanger in the brain of drosophila: phylogenesis, expression and function
Résumé
Hetero(di)meric amino acid transporters (HATs) are one of the most important exchange mechanisms for amino acids. However, only little is known about their concrete function on brain activity. This study focuses on the expression, function and phylogenesis of HATs in fruit flies. HATs are formed by a catalytic "light chain" (SLC7A5-11) and a cofactor called "heavy chain". The genome of Drososphila melanogaster encodes five proteins homologue to mammalian light chains (genderblind, minidiscs, JhI-21, CG9413 and CG1607). All these light chains are highly conserved among several Drosophila species (Reynolds et al, 2009). We used two complementary methods to study the expression of these five candidates in the brain of Drosophila melanogaster. First, we raised antibodies for our transporter candidates. Second, we took advantage of the UAS/Gal4 system. We cloned genomic regions, which putatively contained CIS-regulatory elements in front of Gal4 and generated transgenic animals in which we studied Gal4 induced expression of a (UAS-)reporter gene. The previously identified light chain homologues are expressed by different subsets of glial cells. These subsets include cortex glia, glia forming the blood-brain-barrier and astrocytelike glia. Finally, we present examples of how misexpression of light chains in glia alters neuronal signal transmission. For example, Genderblind expressing glia regulates the extracellular glutamate contend which desensitizes glutamate receptors. It has though a big impact on regulating the strength of glutamatergic signal transmission (Augustin et al.,2007; Grosjean et al, 2008). Another light chain, Minidiscs, is expressed by glia close to brain centers, which are regulating food intake. Consequently, animals mutant for minidiscs are showing deficits in food-odor detection. Taken together our work highlights the importance of glial expressed amino acid exchangers on neuronal activity and behavior.