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Structure and Function of SLC4 Family [Formula: see text] Transporters.

Liu Y, Yang J, Chen LM - Front Physiol (2015)

Bottom Line: Dysfunctions of these transporters are associated with a series of human diseases.Based upon the proposed topology models, mutational and functional studies have identified important structural elements likely involved in the ion translocation by the SLC4 transporters.In the present article, we review the advances during the past decades in understanding the structure and function of the SLC4 transporters.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, Department of Biophysics and Molecular Physiology, School of Life Science and Technology, Huazhong University of Science and Technology Wuhan, China.

ABSTRACT
The solute carrier SLC4 family consists of 10 members, nine of which are [Formula: see text] transporters, including three Na(+)-independent Cl(-)/[Formula: see text] exchangers AE1, AE2, and AE3, five Na(+)-coupled [Formula: see text] transporters NBCe1, NBCe2, NBCn1, NBCn2, and NDCBE, as well as "AE4" whose Na(+)-dependence remains controversial. The SLC4 [Formula: see text] transporters play critical roles in pH regulation and transepithelial movement of electrolytes with a broad range of demonstrated physiological relevances. Dysfunctions of these transporters are associated with a series of human diseases. During the past decades, tremendous amount of effort has been undertaken to investigate the topological organization of the SLC4 transporters in the plasma membrane. Based upon the proposed topology models, mutational and functional studies have identified important structural elements likely involved in the ion translocation by the SLC4 transporters. In the present article, we review the advances during the past decades in understanding the structure and function of the SLC4 transporters.

No MeSH data available.


Phylogenetic tree of SLC4 family. A multiple sequence alignment was performed with human sequences of eAE1 (NP_000333.1), AE2a (NP_003031.3), bAE3 (NP_005061.2), AE4a (NM_031467), NBCe1-A (AAC51645.1), NBCe2-c (AAK97072.1), NBCn1-E (ACH61961), NBCn2-A (NP_071341.2), NDCBE-A (AAY79176), and BTR1 (NP_114423) with the online software Clustal Omega from the European Bioinformatics Institute. The unrooted phylogenetic tree was generated by using Treview based on the sequence alignment (Page, 1996).
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Figure 1: Phylogenetic tree of SLC4 family. A multiple sequence alignment was performed with human sequences of eAE1 (NP_000333.1), AE2a (NP_003031.3), bAE3 (NP_005061.2), AE4a (NM_031467), NBCe1-A (AAC51645.1), NBCe2-c (AAK97072.1), NBCn1-E (ACH61961), NBCn2-A (NP_071341.2), NDCBE-A (AAY79176), and BTR1 (NP_114423) with the online software Clustal Omega from the European Bioinformatics Institute. The unrooted phylogenetic tree was generated by using Treview based on the sequence alignment (Page, 1996).

Mentions: It is fundamentally important to maintain acid-base homeostasis in the body. The solute carrier 4 (SLC4) family represents a major group of bicarbonate transporters. In mammals, the SLC4 family consists of 10 genes. Except for SLC4A11 encoding BTR1 which likely mediates electrogenic Na+-coupled borate transport (Parker et al., 2001; Park et al., 2004) and/or electrogenic NH3/H+ cotransport (Ogando et al., 2013; Zhang et al., 2015; for review, see Patel and Parker, 2015), the other nine (SLC4A1-5 and SLC4A7-10) encode transporters that are either Na+-independent or Na+-dependent (Figure 1). The Na+-independent members include three well characterized anion exchangers (AEs) AE1 (SLC4A1), AE2 (SLC4A2), and AE3 (SLC4A3) conducting electroneutral transmembrane exchange of Cl− and . The Na+-dependent members, commonly known as Na+-coupled transporters (NCBTs), include two electrogenic Na+/ cotransporters NBCe1 (SLC4A4) and NBCe2 (SLC4A5), two electroneutral Na+/ cotransporters NBCn1 (SLC4A7) and NBCn2 (SLC4A10), as well as an electroneutral Na+-driven Cl−/ exchanger NDCBE (SLC4A8). The Na+-dependence of “AE4” (SLC4A9) remains controversial. Several groups have shown evidences that the product of SLC4A9 performs Cl−/ exchange (Tsuganezawa et al., 2001; Ko et al., 2002; Xu et al., 2003). However, Parker et al., observed in a preliminary study that human AE4 mediates Na+-dependent transport rather than Na+-independent Cl−/ exchange (Parker et al., 2002). As shown in Figure 1 and Table 1, the amino acid sequence of “AE4” is more closely related to those of the electrogenic NCBTs. Indeed, on the genomic level, the gene structure (e.g., the exon boundaries) of SLC4A9 is more similar to those of SLC4A4 and SLC4A5 than to those of the three AEs (see review by Parker and Boron, 2013).


Structure and Function of SLC4 Family [Formula: see text] Transporters.

Liu Y, Yang J, Chen LM - Front Physiol (2015)

Phylogenetic tree of SLC4 family. A multiple sequence alignment was performed with human sequences of eAE1 (NP_000333.1), AE2a (NP_003031.3), bAE3 (NP_005061.2), AE4a (NM_031467), NBCe1-A (AAC51645.1), NBCe2-c (AAK97072.1), NBCn1-E (ACH61961), NBCn2-A (NP_071341.2), NDCBE-A (AAY79176), and BTR1 (NP_114423) with the online software Clustal Omega from the European Bioinformatics Institute. The unrooted phylogenetic tree was generated by using Treview based on the sequence alignment (Page, 1996).
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Related In: Results  -  Collection

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Figure 1: Phylogenetic tree of SLC4 family. A multiple sequence alignment was performed with human sequences of eAE1 (NP_000333.1), AE2a (NP_003031.3), bAE3 (NP_005061.2), AE4a (NM_031467), NBCe1-A (AAC51645.1), NBCe2-c (AAK97072.1), NBCn1-E (ACH61961), NBCn2-A (NP_071341.2), NDCBE-A (AAY79176), and BTR1 (NP_114423) with the online software Clustal Omega from the European Bioinformatics Institute. The unrooted phylogenetic tree was generated by using Treview based on the sequence alignment (Page, 1996).
Mentions: It is fundamentally important to maintain acid-base homeostasis in the body. The solute carrier 4 (SLC4) family represents a major group of bicarbonate transporters. In mammals, the SLC4 family consists of 10 genes. Except for SLC4A11 encoding BTR1 which likely mediates electrogenic Na+-coupled borate transport (Parker et al., 2001; Park et al., 2004) and/or electrogenic NH3/H+ cotransport (Ogando et al., 2013; Zhang et al., 2015; for review, see Patel and Parker, 2015), the other nine (SLC4A1-5 and SLC4A7-10) encode transporters that are either Na+-independent or Na+-dependent (Figure 1). The Na+-independent members include three well characterized anion exchangers (AEs) AE1 (SLC4A1), AE2 (SLC4A2), and AE3 (SLC4A3) conducting electroneutral transmembrane exchange of Cl− and . The Na+-dependent members, commonly known as Na+-coupled transporters (NCBTs), include two electrogenic Na+/ cotransporters NBCe1 (SLC4A4) and NBCe2 (SLC4A5), two electroneutral Na+/ cotransporters NBCn1 (SLC4A7) and NBCn2 (SLC4A10), as well as an electroneutral Na+-driven Cl−/ exchanger NDCBE (SLC4A8). The Na+-dependence of “AE4” (SLC4A9) remains controversial. Several groups have shown evidences that the product of SLC4A9 performs Cl−/ exchange (Tsuganezawa et al., 2001; Ko et al., 2002; Xu et al., 2003). However, Parker et al., observed in a preliminary study that human AE4 mediates Na+-dependent transport rather than Na+-independent Cl−/ exchange (Parker et al., 2002). As shown in Figure 1 and Table 1, the amino acid sequence of “AE4” is more closely related to those of the electrogenic NCBTs. Indeed, on the genomic level, the gene structure (e.g., the exon boundaries) of SLC4A9 is more similar to those of SLC4A4 and SLC4A5 than to those of the three AEs (see review by Parker and Boron, 2013).

Bottom Line: Dysfunctions of these transporters are associated with a series of human diseases.Based upon the proposed topology models, mutational and functional studies have identified important structural elements likely involved in the ion translocation by the SLC4 transporters.In the present article, we review the advances during the past decades in understanding the structure and function of the SLC4 transporters.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, Department of Biophysics and Molecular Physiology, School of Life Science and Technology, Huazhong University of Science and Technology Wuhan, China.

ABSTRACT
The solute carrier SLC4 family consists of 10 members, nine of which are [Formula: see text] transporters, including three Na(+)-independent Cl(-)/[Formula: see text] exchangers AE1, AE2, and AE3, five Na(+)-coupled [Formula: see text] transporters NBCe1, NBCe2, NBCn1, NBCn2, and NDCBE, as well as "AE4" whose Na(+)-dependence remains controversial. The SLC4 [Formula: see text] transporters play critical roles in pH regulation and transepithelial movement of electrolytes with a broad range of demonstrated physiological relevances. Dysfunctions of these transporters are associated with a series of human diseases. During the past decades, tremendous amount of effort has been undertaken to investigate the topological organization of the SLC4 transporters in the plasma membrane. Based upon the proposed topology models, mutational and functional studies have identified important structural elements likely involved in the ion translocation by the SLC4 transporters. In the present article, we review the advances during the past decades in understanding the structure and function of the SLC4 transporters.

No MeSH data available.