SLC4A8 Membrane Protein Introduction

Introduction of SLC4A8

SLC4A8 (solute carrier family 4, member 8), also known as NDCBE, is a sodium-driven chloride/bicarbonate exchanger. It is a member of the solute carrier 4 (SLC4) family of HCO3^- transporters that contain products of 11 genes with similar sequences. Most SLC4 members play important roles in regulating intracellular pH. SLC4A8 is highly expressed in all major regions of the brain, spinal column and in testis, with moderate levels in trachea, thyroid and medulla region of kidney, as well as low levels in pancreas and kidney cortex.

Basic Information of SLC4A8
Protein Name	Electroneutral sodium bicarbonate exchanger 1
Gene Name	SLC4A8
Aliases	NBC3, NDCBE
Organism	Homo sapiens (Human)
UniProt ID	Q2Y0W8
Transmembrane Times	11
Length (aa)	1093
Sequence	MPAAGSNEPDGVLSYQRPDEEAVVDQGGTSTILNIHYEKEELEGHRTLYVGVRMPLGRQSHRHHRTHGQKHRRRGRGKGASQGEEGLEALAHDTPSQRVQFILGTEEDEEHVPHELFTELDEICMKEGEDAEWKETARWLKFEEDVEDGGERWSKPYVATLSLHSLFELRSCLINGTVLLDMHANSIEEISDLILDQQELSSDLNDSMRVKVREALLKKHHHQNEKKRNNLIPIVRSFAEVGKKQSDPHLMDKHGQTVSPQSVPTTNLEVKNGVNCEHSPVDLSKVDLHFMKKIPTGAEASNVLVGEVDILDRPIVAFVRLSPAVLLSGLTEVPIPTRFLFILLGPVGKGQQYHEIGRSMATIMTDEIFHDVAYKAKERDDLLAGIDEFLDQVTVLPPGEWDPSIRIEPPKNVPSQEKRKMPGVPNGNVCHIEQEPHGGHSGPELQRTGRLFGGLVLDIKRKAPWYWSDYRDALSLQCLASFLFLYCACMSPVITFGGLLGEATEGRISAIESLFGASMTGIAYSLFAGQALTILGSTGPVLVFEKILFKFCKDYALSYLSLRACIGLWTAFLCIVLVATDASSLVCYITRFTEEAFASLICIIFIYEAIEKLIHLAETYPIHMHSQLDHLSLYYCRCTLPENPNNHTLQYWKDHNIVTAEVHWANLTVSECQEMHGEFMGSACGHHGPYTPDVLFWSCILFFTTFILSSTLKTFKTSRYFPTRVRSMVSDFAVFLTIFTMVIIDFLIGVPSPKLQVPSVFKPTRDDRGWIINPIGPNPWWTVIAAIIPALLCTILIFMDQQITAVIINRKEHKLKKGCGYHLDLLMVAIMLGVCSIMGLPWFVAATVLSITHVNSLKLESECSAPGEQPKFLGIREQRVTGLMIFVLMGCSVFMTAILKFIPMPVLYGVFLYMGVSSLQGIQFFDRLKLFGMPAKHQPDFIYLRHVPLRKVHLFTLIQLTCLVLLWVIKASPAAIVFPMMVLALVFVRKVMDLCFSKRELSWLDDLMPESKKKKLDDAKKKAKEEEEAEKMLEIGGDKFPLESRKLLSSPGKNISCRCDPSEINISDEMPKTTVWKALSMNSGNAKEKSLFN

Function of SLC4A8 Membrane Protein

SLC4A8 (NDCBE) is a sodium-driven chloride/bicarbonate exchanger that mediates the uptake of 1 Na⁺ and 2 HCO3^- in exchange for 1 Cl^-. It plays an important role in cell pH regulation by transporting HCO3^- from blood to cell. And the increased expression of SLC4A8 in severe acid stress could be important for cell survival by mediating the influx of HCO3^- into the cells. It has been found that the high levels of SLC4A8 are focused in multiple CNS neurons including the cerebral cortex, substantial nigra, medulla, cerebellum, and the basolateral membrane of fetal choroid plexus where it contributes to pH(i) regulation. Moreover, SLC4A8 is found to predominantly localize to presynaptic nerve endings where it functions as a key regulator of presynaptic pH involved in synaptic glutamate release and neuronal activity regulation. In addition, SLC4A8 also exerts a role in the regulation of electroneutral Na⁺ reabsorption process in the renal cortical collecting ducts of mice, suggesting a role for the transporter in the mediation of fluid homeostasis in mice.

Fig.1 Phylogenetic tree of SLC4 family. (Ying, 2015)

Application of SLC4A8 Membrane Protein in Literature

Sinning A., et al. Synaptic glutamate release is modulated by the Na⁺-driven Cl^-/HCO3^- exchanger Slc4a8. J Neurosci. 2011, 31(20):7300-11. PubMed ID: 21593314

The article indicates that Slc4a8 is involved in the regulation of synaptic glutamate release in a pH-dependent manner.
Leviel F., et al. The Na⁺-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na⁺ reabsorption process in the renal cortical collecting ducts of mice. Journal of Clinical Investigation. 2010, 120(5):1627-1635. PubMed ID: 20389022

The experimental results support that SLC4A8 plays a role in the regulation of substantial Na⁺ reabsorption in the renal cortical collecting ducts of mice.
Lee H.J., et al. The sodium-driven chloride/bicarbonate exchanger NDCBE in rat brain is upregulated by chronic metabolic acidosis. Brain Research. 2011, 1377(2):13-20. PubMed ID: 21195699

In this study, authors identify that the Na(+)-driven Cl/HCO(3) exchanger NDCBE is upregulated by chronic acid loads in a cell-specific manner.
Chen L.M., et al. Expression and localization of Na-driven Cl-HCO(3)(-) exchanger (SLC4A8) in rodent CNS. Neuroscience. 2008, 153(1):162-174. PubMed ID: 18359573

By means of immunocytochemistry, authors detect the high NDCBE levels in multiple CNS neurons including the cerebral cortex, substantial nigra, medulla, cerebellum, and the basolateral membrane of fetal choroid plexus. Thus, it is proposed that NDCBE is responsible for pH(i) regulation in multiple CNS neurons.
Burette A.C., et al. The sodium-driven chloride/bicarbonate exchanger in presynaptic terminals. Journal of Comparative Neurology. 2012, 520(7):1481-92. PubMed ID: 22102085

The study demonstrates that NDCBE is involved in the regulation of glutamatergic transmission throughout the brain. Besides, it also plays a potential role in regulation of γ-aminobutyric acid (GABA)ergic neurotransmission.

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Reference

Ying L, et al. (2015). Structure and function of SLC4 family HCO3^- transporters. Frontiers in Physiology. 6: 355.

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