The betaine-GABA transporter (BGT1, slc6a12) is predominantly expressed in the liver and at lower levels in the kidneys and at the brain surface

American Journal of Physiology - Renal Physiology - Tập 302 Số 3 - Trang F316-F328 - 2012
Yun Zhou1, Silvia Holmseth2, Rui Hua2, A. C. Lehre2, A M Olofsson2, Irais Poblete-Naredo3, Stephen A. Kempson4, Niels C. Danbolt2
1Centre of Molecular Biology and Neuroscience, Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
2Department of Anatomy; Institute of Basic Medical Sciences, University of Oslo; Oslo Norway
3Departamento de Genética y Biología Molecular, Centro de Investigación y de studios Avanzados del Instituto Politécnico Nacional, México City, Mexico; and
4Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana

Tóm tắt

The Na+- and Cl−-dependent GABA-betaine transporter (BGT1) has received attention mostly as a protector against osmolarity changes in the kidney and as a potential controller of the neurotransmitter GABA in the brain. Nevertheless, the cellular distribution of BGT1, and its physiological importance, is not fully understood. Here we have quantified mRNA levels using TaqMan real-time PCR, produced a number of BGT1 antibodies, and used these to study BGT1 distribution in mice. BGT1 (protein and mRNA) is predominantly expressed in the liver (sinusoidal hepatocyte plasma membranes) and not in the endothelium. BGT1 is also present in the renal medulla, where it localizes to the basolateral membranes of collecting ducts (particularly at the papilla tip) and the thick ascending limbs of Henle. There is some BGT1 in the leptomeninges, but brain parenchyma, brain blood vessels, ependymal cells, the renal cortex, and the intestine are virtually BGT1 deficient in 1- to 3-mo-old mice. Labeling specificity was assured by processing tissue from BGT1-deficient littermates in parallel as negative controls. Addition of 2.5% sodium chloride to the drinking water for 48 h induced a two- to threefold upregulation of BGT1, tonicity-responsive enhancer binding protein, and sodium- myo-inositol cotransporter 1 (slc5a3) in the renal medulla, but not in the brain and barely in the liver. BGT1-deficient and wild-type mice appeared to tolerate the salt treatment equally well, possibly because betaine is one of several osmolytes. In conclusion, this study suggests that BGT1 plays its main role in the liver, thereby complementing other betaine-transporting carrier proteins (e.g., slc6a20) that are predominantly expressed in the small intestine or kidney rather than the liver.

Từ khóa


Tài liệu tham khảo

10.1002/hep.23239

Bagnasco S, 1986, J Biol Chem, 261, 5872, 10.1016/S0021-9258(17)38464-8

10.1016/S0169-328X(00)00034-6

10.1074/jbc.M200374200

10.1046/j.1471-4159.1995.64030977.x

Borden LA, 1995, Receptors Channels, 3, 129

10.1152/physrev.00018.2006

10.1007/s004240050707

10.1016/0005-2736(96)00118-6

10.1523/JNEUROSCI.4178-07.2008

10.1523/JNEUROSCI.22-23-10251.2002

10.1016/S0166-2236(96)10024-2

10.1093/jn/138.9.1641

10.1016/S0301-0082(00)00067-8

10.1016/S0076-6879(98)96028-1

10.1016/0306-4522(92)90316-T

10.1152/ajpregu.00406.2004

10.1006/abbi.2001.2474

10.1002/(SICI)1096-9861(19961216)376:3<431::AID-CNE6>3.0.CO;2-3

10.1152/ajpgi.00238.2009

10.1038/ki.1996.246

10.1016/j.neuroscience.2005.07.022

10.1007/s00429-005-0077-6

10.1016/j.neuroscience.2009.03.048

Holmseth S, J Histochem Cytochem

10.1002/(SICI)1097-4547(19990201)55:3<394::AID-JNR14>3.0.CO;2-E

Kempson SA, 2004, Pflügers Arch, 449, 227

10.1042/BJ20050100

10.1016/j.eplepsyres.2011.02.014

10.1523/JNEUROSCI.18-21-08751.1998

10.1016/S0006-3495(02)75154-0

10.1016/j.clinbiochem.2010.03.009

Liu QR, 1993, J Biol Chem, 268, 2106, 10.1016/S0021-9258(18)53968-5

Lohr JW, 1991, J Am Soc Nephrol, 2, 879, 10.1681/ASN.V24879

López-Corcuera B, 1992, J Biol Chem, 267, 17491, 10.1016/S0021-9258(19)37067-X

10.1073/pnas.0308703100

10.1016/j.neuroscience.2006.06.028

10.1016/j.pharmthera.2009.11.007

10.1042/cs0810551

10.1038/ki.1996.381

10.1152/ajprenal.1997.272.1.F100

10.1152/ajprenal.1991.260.4.F494

10.1007/s11064-005-6879-3

10.1074/jbc.M111.221739

10.1097/01.ASN.0000131520.07008.B3

10.1016/S0005-2736(97)00146-6

10.1002/jnr.10258

10.1523/JNEUROSCI.0338-05.2005

10.1096/fj.02-0456fje

Slow S, 2009, Physiol Res, 58, 403, 10.33549/physiolres.931569

10.1074/jbc.M413027200

10.1097/00004647-200110000-00012

10.1073/pnas.92.4.1072

10.1074/jbc.273.32.20378

10.1152/ajpregu.00003.2008

10.1038/ki.1989.270

10.1159/000303060

10.1152/ajpgi.00249.2009

10.1002/hep.510270235

10.1152/ajprenal.1993.264.6.F948

Yamauchi A, 1992, J Biol Chem, 267, 649, 10.1016/S0021-9258(18)48543-2

10.1152/ajpregu.1990.258.1.R198

10.1023/B:NEUR.0000030698.66675.90

10.1002/jnr.20171

Thông tin
Thông tin xuất bản

American Journal of Physiology - Renal Physiology

Tập 302 Số 3

F316-F328

Thông tin tác giả