The Gene Expression of the Neuronal Protein, SLC38A9, Changes in Mouse Brain After in Vivo Starvation and High-fat Diet

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2017 Feb 25

PMID 28235079

Citations 7

Authors

Sofie V Hellsten

Mikaela M Eriksson

Emilia Lekholm

Vasiliki Arapi

Emelie Perland

Robert Fredriksson

Affiliations

Soon will be listed here.

Abstract

SLC38A9 is characterized as a lysosomal component of the amino acid sensing Ragulator-RAG GTPase complex, controlling the mechanistic target of rapamycin complex 1 (mTORC1). Here, immunohistochemistry was used to map SLC38A9 in mouse brain and staining was detected throughout the brain, in cortex, hypothalamus, thalamus, hippocampus, brainstem and cerebellum. More specifically, immunostaining was found in areas known to be involved in amino acid sensing and signaling pathways e.g. piriform cortex and hypothalamus. SLC38A9 immunoreactivity co-localized with both GABAergic and glutamatergic neurons, but not with astrocytes. SLC38A9 play a key role in the mTORC1 pathway, and therefore we performed in vivo starvation and high-fat diet studies, to measure gene expression alterations in specific brain tissues and in larger brain regions. Following starvation, Slc38a9 was upregulated in brainstem and cortex, and in anterior parts of the brain (Bregma 3.2 to -2.1mm). After high-fat diet, Slc38a9 was specifically upregulated in hypothalamus, while overall downregulation was noticed throughout the brain (Bregma 3.2 to -8.6mm).

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References

Lee J, Dominy Jr J, Sikalidis A, Hirschberger L, Wang W, Stipanuk M . HepG2/C3A cells respond to cysteine deprivation by induction of the amino acid deprivation/integrated stress response pathway. Physiol Genomics. 2008; 33(2):218-29. DOI: 10.1152/physiolgenomics.00263.2007. View

Varoqui H, Zhu H, Yao D, Ming H, Erickson J . Cloning and functional identification of a neuronal glutamine transporter. J Biol Chem. 2000; 275(6):4049-54. DOI: 10.1074/jbc.275.6.4049. View

Perland E, Hellsten S, Lekholm E, Eriksson M, Arapi V, Fredriksson R . The Novel Membrane-Bound Proteins MFSD1 and MFSD3 are Putative SLC Transporters Affected by Altered Nutrient Intake. J Mol Neurosci. 2016; 61(2):199-214. PMC: 5321710. DOI: 10.1007/s12031-016-0867-8. View

Sato H, Nomura S, Maebara K, Sato K, Tamba M, Bannai S . Transcriptional control of cystine/glutamate transporter gene by amino acid deprivation. Biochem Biophys Res Commun. 2004; 325(1):109-16. DOI: 10.1016/j.bbrc.2004.10.009. View

Hara K, Yonezawa K, Weng Q, Kozlowski M, Belham C, Avruch J . Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J Biol Chem. 1998; 273(23):14484-94. DOI: 10.1074/jbc.273.23.14484. View

Hao S, Ross-Inta C, Gietzen D . The sensing of essential amino acid deficiency in the anterior piriform cortex, that requires the uncharged tRNA/GCN2 pathway, is sensitive to wortmannin but not rapamycin. Pharmacol Biochem Behav. 2009; 94(3):333-40. PMC: 3667674. DOI: 10.1016/j.pbb.2009.09.014. View

Schwartz M, Woods S, Porte Jr D, Seeley R, Baskin D . Central nervous system control of food intake. Nature. 2000; 404(6778):661-71. DOI: 10.1038/35007534. View

Cota D . Mammalian target of rapamycin complex 1 (mTORC1) signaling in energy balance and obesity. Physiol Behav. 2009; 97(5):520-4. DOI: 10.1016/j.physbeh.2009.03.006. View

Fernandez J, Lopez A, Wang C, Mishra R, Zhou L, Yaman I . Transcriptional control of the arginine/lysine transporter, cat-1, by physiological stress. J Biol Chem. 2003; 278(50):50000-9. DOI: 10.1074/jbc.M305903200. View

10.

Pinilla J, Aledo J, Cwiklinski E, Hyde R, Taylor P, Hundal H . SNAT2 transceptor signalling via mTOR: a role in cell growth and proliferation?. Front Biosci (Elite Ed). 2011; 3(4):1289-99. DOI: 10.2741/e332. View

11.

Fingar D, Blenis J . Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene. 2004; 23(18):3151-71. DOI: 10.1038/sj.onc.1207542. View

12.

Gonzalez-Gonzalez I, Cubelos B, Gimenez C, Zafra F . Immunohistochemical localization of the amino acid transporter SNAT2 in the rat brain. Neuroscience. 2004; 130(1):61-73. DOI: 10.1016/j.neuroscience.2004.09.023. View

13.

He L, Vasiliou K, Nebert D . Analysis and update of the human solute carrier (SLC) gene superfamily. Hum Genomics. 2009; 3(2):195-206. PMC: 2752037. DOI: 10.1186/1479-7364-3-2-195. View

14.

Ramakers C, Ruijter J, Lekanne Deprez R, Moorman A . Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci Lett. 2003; 339(1):62-6. DOI: 10.1016/s0304-3940(02)01423-4. View

15.

Hundal H, Taylor P . Amino acid transceptors: gate keepers of nutrient exchange and regulators of nutrient signaling. Am J Physiol Endocrinol Metab. 2009; 296(4):E603-13. PMC: 2670634. DOI: 10.1152/ajpendo.91002.2008. View

16.

Maurin A, Jousse C, Averous J, Parry L, Bruhat A, Cherasse Y . The GCN2 kinase biases feeding behavior to maintain amino acid homeostasis in omnivores. Cell Metab. 2005; 1(4):273-7. DOI: 10.1016/j.cmet.2005.03.004. View

17.

Haitina T, Lindblom J, Renstrom T, Fredriksson R . Fourteen novel human members of mitochondrial solute carrier family 25 (SLC25) widely expressed in the central nervous system. Genomics. 2006; 88(6):779-790. DOI: 10.1016/j.ygeno.2006.06.016. View

18.

Bagchi S, Baomar H, Al-Walai S, Al-Sadi S, Fredriksson R . Histological analysis of SLC38A6 (SNAT6) expression in mouse brain shows selective expression in excitatory neurons with high expression in the synapses. PLoS One. 2014; 9(4):e95438. PMC: 3994050. DOI: 10.1371/journal.pone.0095438. View

19.

Padbury J, Diah S, McGonnigal B, Miller C, Fugere C, Kuzniar M . Transcriptional regulation of the LAT-1/CD98 light chain. Biochem Biophys Res Commun. 2004; 318(2):529-34. DOI: 10.1016/j.bbrc.2004.04.062. View

20.

Nakanishi T, Kekuda R, Fei Y, Hatanaka T, Sugawara M, Martindale R . Cloning and functional characterization of a new subtype of the amino acid transport system N. Am J Physiol Cell Physiol. 2001; 281(6):C1757-68. DOI: 10.1152/ajpcell.2001.281.6.C1757. View