A5061056357- Amino Acid Enzymes and Metabolism
- Neuroscience and Neuropharmacology Research
- Drug Transport and Resistance Mechanisms
- Polyamine Metabolism and Applications
- Epigenetics and DNA Methylation
- Pancreatic function and diabetes
- Metabolism and Genetic Disorders
- Regulation of Appetite and Obesity
- Ion Transport and Channel Regulation
- Receptor Mechanisms and Signaling
- Cellular transport and secretion
- Nuclear Receptors and Signaling
- Anesthesia and Neurotoxicity Research
- Adenosine and Purinergic Signaling
- Stress Responses and Cortisol
- Boron Compounds in Chemistry
- Neurotransmitter Receptor Influence on Behavior
- Biochemical Analysis and Sensing Techniques
- Nuclear Physics and Applications
Uppsala University
2013-2022
Membrane-bound solute carriers (SLCs) are essential as they maintain several physiological functions, such nutrient uptake, ion transport and waste removal. The SLC family comprise about 400 transporters, we have identified two new putative members, major facilitator superfamily domain containing 1 (MFSD1) 3 (MFSD3). They cluster phylogenetically with SLCs of MFS type, both proteins conserved in chordates, while MFSD1 is also found fruit fly. Based on homology modelling, predict 12...
In brain cells, glutamine transporters are vital to monitor and control the levels of glutamate GABA . There 11 members SLC 38 family amino acid which eight have been functionally characterized. Here, we report first histological functional characterization previously orphan member, 38A10. We used pairwise global sequence alignments determine identity between members. 38A10 was found share 20–25% transmembrane with several members, predicted helices. immunostaining abundant in mouse using a...
The B0AT2 protein is a product of the SLC6A15 gene belonging to SLC6 subfamily and has been shown be transporter essential branched-chain amino acids. We aimed further characterize in CNS, use Slc6a15 knock out (KO) mice investigate whether important for mediating anorexigenic effect leucine. used KO role brain response leucine particular on food intake. show lower reduction intake as well neuronal activation ventromedial hypothalamic nucleus (VMH) injections compared wild type mice. also...
The vesicular B0AT3 transporter (SLC6A17), one of the members SLC6 family, is a for neutral amino acids and exclusively expressed in brain. Here we provide comprehensive expression profile mouse brain using situ hybridization immunohistochemistry.We confirmed previous data from rat used novel custom made antibody to obtain detailed co-labelling with several cell type specific markers. was highly both inhibitory excitatory neurons. overlapping those glutamate 2 (VGLUT2) 1 (VGLUT1). We also...
Amino acid sensing and signalling is vital for cells, both gene expression protein levels of amino transporters are regulated in response to availability. Here, the aim was study regulation all members SLC38 transporter family, Slc38a1-11, mouse brain cells following starvation. We reanalyzed microarray data immortalized hypothalamic cell line N25/2 subjected complete starvation 1 h, 2 3 5 h or 16 focusing specifically on family. All 11 Slc38 genes were expressed line, Slc38a1, Slc38a2...
SLC18B1 is a sister gene to the vesicular monoamine and acetylcholine transporters, only known polyamine transporter, with unknown physiological role. We reveal that Slc18b1 knock out mice has significantly reduced content in brain providing first evidence functionally required for regulating levels. found this mouse impaired short long term memory novel object recognition, radial arm maze self-administration paradigms. also show KO have altered expression of genes involved Long Term...
Amino acids are known to play a key role in gene expression regulation, and mammalian cells, amino acid signaling is mainly mediated via two pathways, the target of rapamycin complex 1 (mTORC1) pathway responsive (AAR) pathway. It vital for cells have system sense levels, order control protein synthesis catabolism. transporters crucial these due both their sensing transport functions. In this large‐scale study, an immortalized mouse hypothalamic cell line (N25/2) was used study changes...
Characterization of orphan transporters is importance due to their involvement in cellular homeostasis but also pharmacokinetics and pharmacodynamics. The tissue localization, as well function, still unknown for many the solute carriers belonging major facilitator superfamily (MFS) Pfam clan. Here, we have characterized two putative novel MFSD14A (HIAT1) MFSD14B (HIATL1) mouse central nervous system found protein staining throughout adult brain. Both localized neurons co-localized with Golgi...
Out of the 430 known solute carriers (SLC) in humans, 30% are still orphan transporters regarding structure, distribution or function. Approximately one third all SLCs belong to evolutionary conserved and functionally diverse Major Facilitator Superfamily (MFS). Here, we studied proteins, MFSD4A MFSD9, which atypical MFS type. Hidden Markov Models were used identify orthologues several vertebrates, human MFSD9 share high sequence identity with their identified orthologues. also shared more...
Many transporters such as the solute carriers belonging to Major facilitator superfamily Pfam clan are orphans in that their tissue and cellular localization well substrate profile function still unknown. Here we have characterized putative carrier UNC93A. We aimed investigate expression on both protein mRNA level of UNC93A mouse since it has not been clarified. staining was found cortex, hippocampus cerebellum. It be expressed many neurons, but all, with located close proximity plasma...
PAT4, the fourth member of SLC36/proton dependent amino acid transporter (PAT) family, is a high-affinity, low capacity electroneutral neutral acids like proline and tryptophan. It has also been associated with function mTORC1, complex in mammalian target rapamycin (mTOR) pathway. We performed situ hybridization immunohistological analysis to determine expression profile as well an RT-PCR study on tissue from mice exposed leucine. phylogenetic evolutionary origin PAT4. The...
Acetaminophen (AAP; or paracetamol) is a widely used nonprescription drug with antipyretic and analgesic properties. Alarmingly, there an increasing body of evidence showing that developmental exposure to AAP associated adverse behavioural outcomes later in life. We have previously shown relevant doses 10-day-old mice affected memory, learning locomotor activity the adult animals. Interestingly, neurons dentate gyrus (DG) relatively late time origin as they are generated during first two...
SLC38A9 is characterized as a lysosomal component of the amino acid sensing Ragulator-RAG GTPase complex, controlling mechanistic target rapamycin complex 1 (mTORC1). Here, immunohistochemistry was used to map in mouse brain and staining detected throughout brain, cortex, hypothalamus, thalamus, hippocampus, brainstem cerebellum. More specifically, immunostaining found areas known be involved signaling pathways e.g. piriform cortex hypothalamus. immunoreactivity co-localized with both...