Identification of SLC38A7 (SNAT7) Protein as a Glutamine Transporter Expressed in Neurons

被引:97
作者
Hagglund, Maria G. A. [1 ]
Sreedharan, Smitha [1 ]
Nilsson, Victor C. O. [1 ]
Shaik, Jafar H. A. [1 ]
Almkvist, Ingrid M. [1 ]
Backlin, Sofi [1 ]
Wrange, Orjan [2 ]
Fredriksson, Robert [1 ]
机构
[1] Uppsala Univ, Dept Neurosci, S-75124 Uppsala, Sweden
[2] Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden
基金
瑞典研究理事会;
关键词
AMINO-ACID TRANSPORTER; SYSTEM N; NITROGEN-METABOLISM; GLIAL-CELLS; CLONING; LIVER; LOCALIZATION; SUBTYPE; DISTRIBUTIONS; ORGANIZATION;
D O I
10.1074/jbc.M110.162404
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The SLC38 family of transporters has in total 11 members in humans and they encode amino acid transporters called sodium-coupled amino acid transporters (SNAT). To date, five SNATs have been characterized and functionally subdivided into systems A (SLC38A1, SLC38A2, and SLC38A4) and N (SLC38A3 and SLC38A5) showing the highest transport for glutamine and alanine. Here we present identification of a novel glutamine transporter encoded by the Slc38a7 gene, which we propose should be named SNAT7. This transporter has L-glutamine as the preferred substrate but also transports other amino acids with polar side chains, as well as L-histidine and L-alanine. The expression pattern and substrate profile for SLC38A7 shows highest similarity to the known system N transporters. Therefore, we propose that SLC38A7 is a novel member of this system. We used in situ hybridization and immunohistochemistry with a custom-made antibody to show that SLC38A7 is expressed in all neurons, but not in astrocytes, in the mouse brain. SLC38A7 is unique in being the first system N transporter expressed in GABAergic and also other neurons. The preferred substrate and axonal localization of SLC38A7 close to the synaptic cleft indicates that SLC38A7 could have an important function for the reuptake and recycling of glutamate.
引用
收藏
页码:20500 / 20511
页数:12
相关论文
共 59 条
[1]   Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite [J].
Abizaid, Alfonso ;
Liu, Zhong-Wu ;
Andrews, Zane B. ;
Shanabrough, Marya ;
Borok, Erzsebet ;
Elsworth, John D. ;
Roth, Robert H. ;
Sleeman, Mark W. ;
Picciotto, Marina R. ;
Tschop, Matthias H. ;
Gao, Xiao-Bing ;
Horvath, Tamas L. .
JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (12) :3229-3239
[2]  
Abramoff M.D., 2004, Biophotonics International, V11, P36
[3]   Localization and functional relevance of system A neutral amino acid transporters in cultured hippocampal neurons [J].
Armano, S ;
Coco, S ;
Bacci, A ;
Pravettoni, E ;
Schenk, U ;
Verderio, C ;
Varoqui, H ;
Erickson, JD ;
Matteoli, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (12) :10467-10473
[4]   THE IDENTIFICATION OF NEUTRAL AMINO-ACID-TRANSPORT SYSTEMS [J].
BARKER, GA ;
ELLORY, JC .
EXPERIMENTAL PHYSIOLOGY, 1990, 75 (01) :3-26
[5]   Transfer of glutamine between astrocytes and neurons [J].
Bröer, S ;
Brookes, N .
JOURNAL OF NEUROCHEMISTRY, 2001, 77 (03) :705-719
[6]   The glutamine commute: take the N line and transfer to the A [J].
Chaudhry, FA ;
Reimer, RJ ;
Edwards, RH .
JOURNAL OF CELL BIOLOGY, 2002, 157 (03) :349-355
[7]   Glutamine uptake by neurons: Interaction of protons with system a transporters [J].
Chaudhry, FA ;
Schmitz, D ;
Reimer, RJ ;
Larsson, P ;
Gray, AT ;
Nicoll, R ;
Kavanaugh, M ;
Edwards, RH .
JOURNAL OF NEUROSCIENCE, 2002, 22 (01) :62-72
[8]   Molecular analysis of system N suggests novel physiological roles in nitrogen metabolism and synaptic transmission [J].
Chaudhry, FA ;
Reimer, RJ ;
Krizaj, D ;
Barber, D ;
Storm-Mathisen, J ;
Copenhagen, DR ;
Edwards, RH .
CELL, 1999, 99 (07) :769-780
[9]   ON THE STRATEGY OF KINETIC DISCRIMINATION OF AMINO-ACID TRANSPORT-SYSTEMS [J].
CHRISTENSEN, HN .
JOURNAL OF MEMBRANE BIOLOGY, 1985, 84 (02) :97-103
[10]   ROLE OF AMINO-ACID-TRANSPORT AND COUNTERTRANSPORT IN NUTRITION AND METABOLISM [J].
CHRISTENSEN, HN .
PHYSIOLOGICAL REVIEWS, 1990, 70 (01) :43-77