Transfer of glutamine between astrocytes and neurons

Journal of Neurochemistry - Tập 77 Số 3 - Trang 705-719 - 2001
Stefan Bröer1, Neville Brookes2
1Division of Biochemistry and Molecular Biology, Faculty of Science, Australian National University, Canberra, Australia
2Department of Pharmacology and Experimental Therapeutics University of Maryland School of Medicine Baltimore, Maryland, USA

Tóm tắt

The export of glutamine from astrocytes, and the uptake of glutamine by neurons, are integral steps in the glutamate‐glutamine cycle, a major pathway for the replenishment of neuronal glutamate. We review here the functional and molecular identification of the transporters that mediate this transfer. The emerging picture of glutamine transfer in adult brain is of a dominant pathway mediated by system N transport (SN1) in astrocytes and system A transport (SAT/ATA) in neurons. The participating glutamine transporters are functionally and structurally related, sharing the following properties: (a) unlike many neutral amino acid transporters which have proven to be obligate exchangers, these glutamine transporters mediate net substrate transfer energized by coupling to ionic gradients; (b) they are sensitive to small pH changes in the physiological range; (c) they are susceptible to adaptive and humoral regulation; (d) they are related structurally to the AAAP (amino acid and auxin permeases) family of transporters. A key difference between SN1 and the SAT/ATA transporters is the ready reversibility of glutamine fluxes via SN1 under physiological conditions, which allows SN1 both to sustain a glutamine concentration gradient in astrocytes and to mediate the net outward flux of glutamine. It is likely that the ASCT2 transporter, an obligate exchanger of neutral amino acids, displaces the SN1 transporter as the main carrier of glutamine export in proliferating astrocytes.

Từ khóa


Tài liệu tham khảo

10.1152/ajpendo.1993.264.6.E993

10.1016/0028-3908(89)90183-4

Arriza J. L., 1993, Cloning and expression of a human neutral amino acid transporter with structural similarity to the glutamate transporter gene family, J. Biol. Chem., 268, 15329, 10.1016/S0021-9258(18)82257-8

10.1111/j.1471-4159.1975.tb03650.x

10.1038/311308b0

10.1113/expphysiol.1990.sp003382

10.1007/BF00965703

10.1523/JNEUROSCI.18-19-07709.1998

10.1126/science.211586

10.1002/hep.1840210236

10.1042/bj3120863

Bröer A., 1999, The astroglial ASCT2 amino acid transporter as a mediator of glutamine efflux, J. Neurochem., 73, 2184, 10.1046/j.1471-4159.1999.02184.x

10.1042/bj3490787

10.1042/0264-6021:3460705

10.1111/j.1471-4159.1988.tb01177.x

10.1111/j.1471-4159.1992.tb08343.x

10.1016/0304-3940(92)90579-V

10.1111/j.1471-4159.1992.tb08895.x

10.1111/j.1471-4159.1993.tb13421.x

10.1016/s0197-0186(00)00015-2

10.1152/ajpcell.1994.267.6.C1633

10.1074/jbc.274.41.28845

10.1016/0896-6273(95)90158-2

10.1016/S0092-8674(00)81674-8

10.1016/0301-0082(90)90034-E

Christensen H. N., 1972, On the meaning of effects of substrate structure on biological transport, Bioenergetics, 4, 233

10.1016/0304-4157(84)90012-1

10.1152/physrev.1990.70.1.43

Christensen H. N., 1967, A distinct Na+‐requiring transport system for alanine, serine, cysteine, and similar amino acids, J. Biol. Chem., 242, 5237, 10.1016/S0021-9258(18)99417-2

10.1146/annurev.nu.07.070187.000451

10.1016/s0197-0186(00)00017-6

10.1097/00004647-200011000-00005

Dykes‐Hoberg M., 2000, Localization of the neutral amino acid transporters ASCT1 and ASCT2 in the rat CNS, Soc. Neurosci. Abstract, 26, 150.12

10.1046/j.1471-4159.1998.71062565.x

10.1016/0301-0082(90)90013-7

10.1111/j.1471-4159.1990.tb04911.x

10.1074/jbc.M002282200

10.1074/jbc.275.13.9690

10.1016/0306-4522(94)90343-3

10.1073/pnas.97.7.3230

10.1523/JNEUROSCI.20-04-01342.2000

10.1097/00004647-199711000-00012

10.1016/0304-3940(80)90109-3

10.1002/(SICI)1097-4547(19990815)57:4<417::AID-JNR1>3.0.CO;2-N

10.1016/0006-8993(95)01442-X

10.1007/BF00972489

10.1016/0165-0270(85)90107-4

10.1126/science.663619

10.1074/jbc.273.37.23629

10.1074/jbc.M000634200

10.1074/jbc.271.31.18657

10.1016/0968-0004(86)90138-6

10.1016/S0021-9258(19)85625-9

10.1046/j.1471-4159.1995.65020871.x

10.1152/ajpcell.1998.274.4.C1101

10.1523/JNEUROSCI.18-21-08751.1998

10.1073/pnas.220256497

10.1042/bj3300255

10.1042/bj2990321

10.1126/science.283.5401.496

10.1038/26246

10.1097/00001756-200011090-00021

Munoz P., 1992, Vanadate stimulates system A amino acid transport activity in skeletal muscle. Evidence for the involvement of intracellular pH as a mediator of vanadate action, J. Biol. Chem., 267, 10381, 10.1016/S0021-9258(19)50030-8

10.1046/j.1471-4159.1996.66041665.x

10.1016/0006-8993(79)90071-4

Oldendorf W. H., 1971, Brain uptake of radiolabeled amino acids, amines, and hexoses after arterial injection, Am. J. Physiol., 221, 1629, 10.1152/ajplegacy.1971.221.6.1629

10.1016/S0021-9258(19)75327-7

10.1152/physrev.1998.78.4.969

10.1111/j.1471-4159.1985.tb07173.x

10.1091/mbc.10.12.4135

10.1074/jbc.274.28.19738

10.1016/0306-4522(94)90249-6

10.1016/S0005-2736(99)00224-2

10.1016/0006-8993(82)90909-X

10.1073/pnas.140152797

10.1021/bi00446a018

10.1074/jbc.274.49.34948

10.1016/0896-6273(94)90038-8

10.1074/jbc.270.25.14913

10.1016/S0074-7742(08)60289-5

10.1074/jbc.274.28.19745

Shafqat S., 1993, Cloning and expression of a novel Na+‐dependent neutral amino acid transporter structurally related to mammalian Na+/glutamate cotransporters, J. Biol. Chem., 268, 15351, 10.1016/S0021-9258(18)82263-3

10.1073/pnas.96.14.8235

10.1073/pnas.95.1.316

10.1093/jn/130.4.1016S

10.1111/j.1471-4159.1987.tb01039.x

10.1016/0197-0186(93)90064-C

Speciale C., 1989, High‐affinity uptake of l‐kynurenine by a Na+‐independent transporter of neutral amino acids in astrocytes, J. Neurosci., 9, 2066, 10.1523/JNEUROSCI.09-06-02066.1989

10.1046/j.1471-4159.1995.64052125.x

10.1016/s0006-8993(97)00139-x

10.1074/jbc.C000205200

10.1016/S0005-2736(00)00349-7

10.1016/0005-2736(95)00259-6

10.1046/j.1471-4159.1997.68030954.x

Tan C. H., 1987, Sodium‐independent synaptosomal uptake of leucine, Biochem. Int., 14, 161

10.1074/jbc.273.49.32437

10.1074/jbc.271.25.14883

10.1042/bj1230211

10.1074/jbc.275.6.4049

10.1007/s002329900595

10.1006/bbrc.2000.3061

10.1111/j.1471-4159.1986.tb02863.x

Weissbach L., 1982, Evidence for two Na+‐independent neutral amino acid transport systems in primary cultures of rat hepatocytes: time‐dependent changes in activity, J. Biol. Chem., 257, 12006, 10.1016/S0021-9258(18)33668-8

10.1159/000111288

10.1002/(sici)1097-4547(19980315)51:6<675::aid-jnr2>3.3.co;2-n

10.1016/s0306-4522(98)00063-3

10.1074/jbc.M002965200

10.1016/S0005-2736(98)00196-5

10.1111/j.1471-4159.1988.tb01820.x

10.1074/jbc.271.45.27991

10.1113/jphysiol.1996.sp021393

Thông tin
Thông tin xuất bản

Journal of Neurochemistry

Tập 77 Số 3

705-719

Thông tin tác giả