SAT1, A Glutamine Transporter, is Preferentially Expressed in GABAergic Neurons

Subsets of GABAergic neurons are able to maintain high frequency discharge patterns, which requires efficient replenishment of the releasable pool of GABA. Although glutamine is considered a preferred precursor of GABA, the identity of transporters involved in glutamine uptake by GABAergic neurons remains elusive. Molecular analyses revealed that SAT1 (Slc38a1) features system A characteristics with a preferential affinity for glutamine, and that SAT1 mRNA expression is associated with GABAergic neurons. By generating specific antibodies against SAT1 we show that this glutamine carrier is particularly enriched in GABAergic neurons. Cellular SAT1 distribution resembles that of GAD67, an essential GABA synthesis enzyme, suggesting that SAT1 can be involved in translocating glutamine into GABAergic neurons to facilitate inhibitory neurotransmitter generation

The Drosophila G9a gene encodes a multi-catalytic histone methyltransferase required for normal development

Mammalian G9a is a histone H3 Lys-9 (H3–K9) methyltransferase localized in euchromatin and acts as a co-regulator for specific transcription factors. G9a is required for proper development in mammals as g9a(−)/g9a(−) mice show growth retardation and early lethality. Here we describe the cloning, the biochemical and genetical analyses of the Drosophila homolog dG9a. We show that dG9a shares the structural organization of mammalian G9a, and that it is a multi-catalytic histone methyltransferase with specificity not only for lysines 9 and 27 on H3 but also for H4. Surprisingly, it is not the H4–K20 residue that is the target for this methylation. Spatiotemporal expression analyses reveal that dG9a is abundantly expressed in the gonads of both sexes, with no detectable expression in gonadectomized adults. In addition we find a low but clearly observable level of dG9a transcript in developing embryos, larvae and pupae. Genetic and RNAi experiments reveal that dG9a is involved in ecdysone regulatory pathways

G9a, a putative histone methyl-transferase in Drosophila interacts with Tungus, a protein associated with α-Actinin

Histone lysine methylation is considered to be a relatively stable modification associated with important functions in epigenetic gene control and for organizing chromatin domains. Genes encoding mammalian homologues of the Drosophila suppressor of PEV Su(var)3-9 were the first shown to encode proteins with histone lysine methyl-transferase (HKMT) activity. A hallmark signature of this class of proteins is the evolutionary conserved SET-domain found in numerous chromatin regulators, and was named for its occurrence in genes encoding three such regulators in Drosophila, namely Su(var)3-9, E(z) and trithorax. Here we describe the characterization of a putative SET-domain gene in Drosophila melanogaster, G9a. The gene encodes a protein of 1637 amino acids with similar domain architecture as the mammalian homologue of same name. Whole mount in situ hybridization shows that the gene is maternal and immunostaining shows nuclear localization of DmG9a. A yeast two-hybrid screening revealed that DmG9a interacts with Tungus, a LIM-domain protein associated with α-Actinin. Further analysis is needed to investigate the functional implications of this putative interaction

"We have the power". A study of what characterizes leadership of knowledge workers

Master in Business Administration (MBA) - Nord universitet 202

Slc38a1 Conveys Astroglia-Derived Glutamine into GABAergic Interneurons for Neurotransmitter GABA Synthesis

GABA signaling is involved in a wide range of neuronal functions, such as synchronization of action potential firing, synaptic plasticity and neuronal development. Sustained GABA signaling requires efficient mechanisms for the replenishment of the neurotransmitter pool of GABA. The prevailing theory is that exocytotically released GABA may be transported into perisynaptic astroglia and converted to glutamine, which is then shuttled back to the neurons for resynthesis of GABA—i.e., the glutamate/GABA-glutamine (GGG) cycle. However, an unequivocal demonstration of astroglia-to-nerve terminal transport of glutamine and the contribution of astroglia-derived glutamine to neurotransmitter GABA synthesis is lacking. By genetic inactivation of the amino acid transporter Solute carrier 38 member a1 (Slc38a1)—which is enriched on parvalbumin+ GABAergic neurons—and by intraperitoneal injection of radiolabeled acetate (which is metabolized to glutamine in astroglial cells), we show that Slc38a1 mediates import of astroglia-derived glutamine into GABAergic neurons for synthesis of GABA. In brain slices, we demonstrate the role of Slc38a1 for the uptake of glutamine specifically into GABAergic nerve terminals for the synthesis of GABA depending on demand and glutamine supply. Thus, while leaving room for other pathways, our study demonstrates a key role of Slc38a1 for newly formed GABA, in harmony with the existence of a GGG cycle