A family of mammalian anion transportersand their involvement in human genetic diseases

Everett, Lorraine A.; Green, Eric D.

doi:10.1093/hmg/8.10.1883

Cited by 122 publications

(69 citation statements)

References 81 publications

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“…The SLC26A4 protein is mainly expressed in the thyroid gland, inner ear and the kidney, and its malfunction leads to Pendred syndrome (PS; OMIM 274600), a disease often characterized by prelingual deafness and/or goiter (24,25). The detailed function of the SLC26A4 protein is still elusive.…”

Section: Discussionmentioning

confidence: 99%

The expression of wild-type pendrin (SLC26A4) in human embryonic kidney (HEK 293 Phoenix) cells leads to the activation of cationic currents

Dossena¹,

Maccagni²,

Vezzoli³

et al. 2005

eur j endocrinol

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Objective: The SLC26A4 protein (pendrin) seems to be involved in the exchange of chloride with other anions, therefore being responsible for iodide organification in the thyroid gland and the conditioning of the endolymphatic fluid in the inner ear. Malfunction of SLC26A4 leads to Pendred syndrome, characterized by mild thyroid dysfunction often associated with goiter and/or prelingual deafness. The precise function of the SLC26A4 protein, however, is still elusive. An open question is still whether the SLC26A4-induced ion exchange mechanism is electrogenic or electroneutral. Recently, it has been shown that human pendrin expressed in monkey cells leads to chloride currents. Methods: We overexpressed the human SLC26A4 isoform in HEK293 Phoenix cells and measured cationic and anionic currents by the patch-clamp technique in whole cell configuration. Results: Here we show that human pendrin expressed in human cells does not lead to the activation of chloride currents, but, in contrast, leads to an increase of cationic currents. Conclusion: Our experiments suggest that the SLC26A4-induced chloride transport is electroneutral when expressed in human cellular systems.European Journal of Endocrinology 153 693-699

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Section: Discussionmentioning

confidence: 99%

The expression of wild-type pendrin (SLC26A4) in human embryonic kidney (HEK 293 Phoenix) cells leads to the activation of cationic currents

Dossena¹,

Maccagni²,

Vezzoli³

et al. 2005

eur j endocrinol

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“…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). SO 4 2Ϫ deficiency in chondrocytes causes phenotypes (chondrodysplasias) that are characterized by severe growth abnormalities (24). Elevated plasma SO 4 2Ϫ can cause diuresis and acidosis (18), and increased SO 4 2Ϫ concentration ( [SO 4 2Ϫ ]) in the renal tubule lumen reduces Ca 2ϩ and Mg 2ϩ reabsorption (66).…”

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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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“…A pendrina, cambiador aniônico recentemente identificado, pode facilitar o transporte do iodeto através da membrana apical (5,6). Na face luminal desta última, a tireoperoxidase (TPO) oxida o iodeto e, subseqüente-mente, introduz o iodo em resíduos tirosil da tireoglobulina (Tg) intrafolicular [incorporação de iodeto].…”

unclassified

Hipotireoidismo Congênito: Recentes Avanços em Genética Molecular

Rubio¹,

Knobel²,

Nascimento³

et al. 2002

Arq Bras Endocrinol Metab

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RESUMOO hipotireoidismo congênito (HC), detectado em recém-nascidos rastreados ao nascer, é causado por anomalias na organogênese (agenesia, tireóide ectópica, hipoplasia tireóidea) ou por defeitos específicos na hormonogênese. Mais raramente, o hipotireoidismo congênito tem origem em defeitos genéticos centrais, localizados no eixo hipotálamo-hipófise ou em mutações do gene do TSH-beta ou no receptor de TSH. Defeitos específicos da hormonogênese são causados por mutações no gene codificador para a proteína transportadora de iodeto (NIS), no gene da peroxidase (TPO), no gene traduzindo a pendrina (síndrome de Pendred), no gene da tireoglobulina, além de mutações que afetam o receptor de hormônio tireóideo (resistência genética ao HT) ou aos vários defeitos no transporte de HT na circulação periférica. Na maioria dos casos, os defeitos genéticos indicados criam condições para fenótipo com bócio e grau variável de hipotireoidismo, podendo a mutação genética ter expressão variável durante a vida adulta. Congenital hypothyroidism (CH), as seen in the neonatal period, is predominantly caused by defects in the organogenesis (athyreosis, ectopic thyroid, thyroid hypoplasia) or by specific defects in hormonogenesis (dyshormonogenesis). Central hypothyroidism is rare, being linked to specific transcription factors involved in the maturation of the hypothalamic-pituitary axis or by mutations in the TSH-beta gene. Dyshormonogenesis may be caused by mutation coding for thyroid proteins such as the TSH receptor, the sodium-iodide symporter (NIS), the pendrin (Pendred's syndrome), thyroid peroxidase (TPO), thyroglobulin (Tg), thyroid dehalogenase, the receptor for thyroid hormone (TR-beta) or thyroid transport proteins (TBG, transthyretin). Usually, most of these defective genes will induce a phenotype with goiter and variable degree of hypothyroidism that may be present in the neonatal period or will gradually develop during post-natal life. Moreover, the genetic expression may be partial or total according to the specific mutation occurring in the involved genes.

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A family of mammalian anion transportersand their involvement in human genetic diseases

Cited by 122 publications

References 81 publications

The expression of wild-type pendrin (SLC26A4) in human embryonic kidney (HEK 293 Phoenix) cells leads to the activation of cationic currents

The expression of wild-type pendrin (SLC26A4) in human embryonic kidney (HEK 293 Phoenix) cells leads to the activation of cationic currents

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

Hipotireoidismo Congênito: Recentes Avanços em Genética Molecular

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