Functional Analysis of Diastrophic Dysplasia Sulfate Transporter

Satoh, Hideshi; Susaki, Masakazu; Shukunami, Chisa; Iyama, Ken‐ichi; Negoro, Takaharu; Hiraki, Yuji

doi:10.1074/jbc.273.20.12307

Cited by 122 publications

(55 citation statements)

References 33 publications

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“…In contrast to the other proteins studied, expression of the SLC26A2 protein was found strictly in the cilia of the ciliated cells in the efferent ducts. As an epithelial Cl K =SO 2K 4 exchanger (Satoh et al 1998), its putative role in the male reproductive tract is less clear. However, diastrophic dysplasia male patients with mutations in SLC26A2 have not been reported to be subfertile, thus the function of SLC26A2 in male fertility may be less crucial than SLC26A3's, which causes male subfertility when mutated .…”

Section: Discussionmentioning

confidence: 99%

Expression of ion transport-associated proteins in human efferent and epididymal ducts

Kujala¹,

Hihnala²,

Tienari³

et al. 2007

Reproduction

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Appropriate intraluminal microenvironment in the epididymis is essential for maturation of sperm. To clarify whether the anion transporters SLC26A2, SLC26A6, SLC26A7, and SLC26A8 might participate in generating this proper intraluminal milieu, we studied the localization of these proteins in the human efferent and the epididymal ducts by immunohistochemistry. In addition, immunohistochemistry of several SLC26-interacting proteins was performed: the Na C /H C exchanger 3 (NHE3), the Cl K channel cystic fibrosis transmembrane conductance regulator (CFTR), the proton pump V-ATPase, their regulator Na C /H C exchanger regulating factor 1 (NHERF-1), and carbonic anhydrase II (CAII). Our results show that SLC26A6, CFTR, NHE3, and NHERF-1 are co-expressed on the apical side of the nonciliated cells, and SLC26A2 appears in the cilia of the ciliated cells in the human efferent ducts. In the epididymal ducts, SLC26A6, CFTR, NHERF-1, CAII, and V-ATPase (B and E subunits) were co-localized to the apical mitochondria rich cells, while SLC26A7 was expressed in a subgroup of basal cells. SLC26A8 was not found in the structures studied. This is the first study describing the localization of SLC26A2, A6 and A7, and NHERF-1 in the efferent and the epididymal ducts. Immunolocalization of human CFTR, NHE3, CAII, and V-ATPase in these structures differs partly from previous reports from rodents. Our findings suggest roles for these proteins in male fertility, either independently or through interaction and reciprocal regulation with co-localized proteins shown to affect fertility, when disrupted. Reproduction (2007) 133 775-784

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Section: Discussionmentioning

confidence: 99%

Expression of ion transport-associated proteins in human efferent and epididymal ducts

Kujala¹,

Hihnala²,

Tienari³

et al. 2007

Reproduction

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“…In addition, SLC26A1 exhibits Cl Ϫ transport activity when expressed in Xenopus oocytes (45). SLC26A2 (DTDST), which appears to be expressed ubiquitously (32), has affinities for many anions, including SO 4 2Ϫ , HCO 3 Ϫ , Cl Ϫ , oxalate, and S 2 O 3 2Ϫ (79). The putative Cl Ϫ / formate exchanger SLC26A6 (PAT-1, CFEX) has been localized to the BBM of mammalian renal proximal tubule cells (43).…”

Section: Tubular Somentioning

confidence: 99%

Role of tubular secretion and carbonic anhydrase in vertebrate renal sulfate excretion

Pelis¹,

Renfro²

2004

American Journal of Physiology-Regulatory, Integrative and Comp

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/HCO 3 Ϫ exchange at the brushborder membrane, tubular carbonic anhydrase (CA) activity, CAII protein, and a proportion of tubular SO 4 2Ϫ secretion that is CA dependent. CA activity is required for about one-half of this net SO 4 2Ϫ secretion but is also required for about one-half of the net reabsorption in bird proximal epithelium. A CA-SO 4 2Ϫ /anion exchanger metabolon arrangement is proposed that may speed both the secretory and reabsorptive processes. renal proximal tubule; transport metabolon INORGANIC SO 4 2Ϫ IS THE SECOND most abundant anion in the sea and one of the most abundant anions in vertebrate plasma, with concentrations varying among species from 0.3 to 1.8 mM. This large tetrahedral divalent anion can be obtained from the diet (83) or oxidation of the sulfur-containing amino acids cysteine and methionine (77). Sulfoconjugation reactions are the initial detoxification process for many endogenous (e.g., steroid hormones) and xenobiotic compounds and are required for the activation of numerous biological molecules (e.g., heparin, cholecystokinin, and gastrin) (59). SO 4 2Ϫ is a major component of glycosaminoglycans (dermatan sulfate, chondroitin sulfate, keratan sulfate, and heparan sulfate), which are structural components of numerous tissues, including cartilage, bone, myelin, and basal lamina (40 ]) in the renal tubule lumen reduces Ca 2ϩ and Mg 2ϩ reabsorption (66). RENAL SULFATE CLEARANCEThe kidneys are the major avenue for SO 4 2Ϫ excretion in vertebrates. Nearly all of plasma SO 4 2Ϫ is ultrafilterable in mammals (4), whereas 80% and 47% of plasma SO 4 2Ϫ are ultrafilterable in birds (71) and fish (75), respectively. Variation in the estimates of the ultrafilterable fraction of plasma SO 4 2Ϫ in vertebrates may arise from species differences or variations in method of determination. Urine content is determined by glomerular filtration, tubular reabsorption, and tubular secretion. This review will focus on the latter and will provide only a brief overview of tubular reabsorption because it has been described in detail elsewhere (2,51,52,57).Reabsorption of filtered SO 4 2Ϫ occurs primarily in the proximal tubule (35) secretion does not occur in these animals. SO 4 2Ϫ loading apparently has no effect on the saturable reabsorptive transport maximum for SO 4 2Ϫ (Tm SO 4 2Ϫ ) in the renal tubule of the human, dog, and frog (3,28,48). In contrast, Tm SO 4 2Ϫ in rats is reduced ϳ50% after plasma SO 4 2Ϫ loading, indicating that adaptive mechanisms are in place to depress reabsorption, thus increasing excretion (27). Similarly, in domestic fowl, Tm SO 4 2Ϫ decreases with plasma SO 4 2Ϫ loading, leading to the conclusion that a fraction of the excreted SO 4 2Ϫ is the result of tubular secretion (30). Thiosulfate, an inhibitor of SO 4 2Ϫ transporters,

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“…Transport activity was assayed by measuring the efflux of sulfate ( 35 SO 4 ) as described (21,22) or iodide ( 125 I) as described previously (23). All experiments were performed at 37°C in 12-well plates.…”

Section: S]methionine In a Rabbit Reticulocyte Lysate (Promega)mentioning

confidence: 99%

Tat1, a Novel Sulfate Transporter Specifically Expressed in Human Male Germ Cells and Potentially Linked to RhoGTPase Signaling

Touré

Morin

Pineau

et al. 2001

Journal of Biological Chemistry

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RhoGTPases (Rho, Rac, and Cdc42) are known to regulate multiple functions, including cell motility, adhesion, and proliferation; however, the signaling pathways underlying these pleiotropic effects are far from fully understood. We have recently described a new RhoGAP (GTPase activating protein for RhoGTPases) gene, MgcRacGAP, primarily expressed in male germ cells, at the spermatocyte stage. We report here the isolation, through two-hybrid cloning, of a new partner of MgcRacGAP, very specifically expressed in the male germ line and showing structural features of anion transporters. This large protein (970 amino acids and a predicted size of 109 kDa), we provisionally designated Tat1 (for testis anion transporter 1), is closely related to a sulfate permease family comprising three proteins in human (DRA, Pendrin, and DTD); it is predicted to be an integral membrane protein with 14 transmembrane helices and intracytoplasmic NH 2 and COOH termini. In situ hybridization studies demonstrate that Tat1 and MgcRacGAP genes are coexpressed in male germ cells at the spermatocyte stage. On testis sections, Tat1 protein can be immunodetected in spermatocytes and spermatids associated with plasma membrane. Two-hybrid and in vitro binding assays demonstrate that MgcRacGAP stably interacts through its NH 2 -terminal domain with the Tat1 COOH-terminal region. Expression of Tat1 protein in COS7 cells generates a 4,4-diisothiocyano-2,2-disulfonic acid stilbene and chloride-sensitive sulfate transport. Therefore we conclude that Tat1 is a novel sulfate transporter specifically expressed in spermatocytes and spermatids and interacts with MgcRacGAP in these cells. These observations raise the possibility of a new regulatory pathway linking sulfate transport to Rho signaling in male germ cells.

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Functional Analysis of Diastrophic Dysplasia Sulfate Transporter

Cited by 122 publications

References 33 publications

Expression of ion transport-associated proteins in human efferent and epididymal ducts

Expression of ion transport-associated proteins in human efferent and epididymal ducts

Role of tubular secretion and carbonic anhydrase in vertebrate renal sulfate excretion

Tat1, a Novel Sulfate Transporter Specifically Expressed in Human Male Germ Cells and Potentially Linked to RhoGTPase Signaling

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