Murine chromosome 16 telomeric region, homologous with human chromosome 21q22, contains the osmoregulatory Na&lt;sup&gt;+&lt;/sup&gt;/myo-inositol cotransporter (SLC5A3) gene

McVeigh, K.E.; Mallee, John; Lucente, A.; Barnoski, Barry L.; Wu, Shuang; Berry, Gerard T.

doi:10.1159/000015509

Cited by 14 publications

(7 citation statements)

References 38 publications

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“…The protein was characterised in Xenopus oocytes and showed strong similarity to Na + /glucose transporters [45]. The so‐called SMIT (Sodium/ Myo ‐Inositol Transporter; later re‐named in SMIT1 after discovery of a second Na + ‐coupled inositol transporter) was soon found also in rat [104], human [7] and mouse [58]. The respective gene for SMIT1, SLC5A3 , belongs to the Solute Carrier Family 5 (SLC5A) [7].…”

Section: Sodium Ion Coupled Inositol Transportersmentioning

confidence: 99%

Inositol transport proteins

Schneider

2015

FEBS Letters

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a b s t r a c tThe cyclic polyol myo-inositol is a key molecule in many different metabolic pathways among all organisms; in addition, it is fundamental for osmotic balance in the mammalian brain. This review sums up inositol transporters from eukaryotic organisms, elucidating their vital role in regulating the intracellular distribution and uptake of inositol. They can be divided into two groups according to their transport mechanisms: (1) sodium ion coupled inositol transporters that belong to the Solute Carrier Families 5 and 6-like Superfamily and, (2) proton coupled inositol symporters that are members of the Major Facilitator Superfamily. Intriguingly members of both families offer promising targets for medical treatment of a variety of diseases.

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Section: Sodium Ion Coupled Inositol Transportersmentioning

confidence: 99%

Inositol transport proteins

Schneider

2015

FEBS Letters

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“…Myo-inositol is transported into a cell by a sodium/myoinositol cotransport protein, SLC5A3, a member of the solute carrier (SLC) superfamily of sugar transport proteins [20]. In the mouse, this protein is composed of 718 amino acids and is proposed to have 14 transmembrane domains.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the Expression and Regulation of Genes Necessary for myo-Inositol Biosynthesis and Transport in the Seminiferous Epithelium1

Chauvin

Griswold

2004

Biology of Reproduction

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In many mammals, the concentration of myo-inositol in the fluid of the seminiferous tubules is dramatically higher than levels found in serum. Two enzymes involved in myo-inositol synthesis: myo-inositol-1-phosphate synthase (ISYNA1) and myo-inositol monophosphatase-1 (IMPA1), are known to have high activity in the testes. ISYNA1 is an isomerase that catalyzes the conversion of glucose-6-phoshate to myo-inositol-1-phosphate. IMPA1 then hydrolyzes the phosphate group to produce myo-inositol. Although no physiological role for the high concentration of myo-inositol has yet to be elucidated, it has been suggested that it could be involved in osmoregulation. Previous research on these enzymes in the testis has focused on enzyme activity. The objective of this study was to evaluate the expression of these genes and the myo-inositol transporter, Slc5a3, within the testis. Using Northern blot analyses, we found that all three genes, Impa1, Isyna1, and Slc5a3 are expressed in Sertoli cells. Isyna1 is highly expressed in two types of germ cells, pachytene spermatocytes and round spermatids. IMPA1 was expressed in round spermatids. Slc5a3 expression is upregulated when Sertoli cells are treated with 0.1 mM dibutyryl cAMP. When Sertoli cells were cultured in a hypertonic medium, there was an increase in the expression of Isyna1 and Slc5a3. We postulate that this upregulation is a result of the capability of the Sertoli cell to sense and then react to a change in osmolarity by increasing the transport and production of the osmolyte myo-inositol.

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“…This is suggested by the following findings : humans with trisomy 21 (Down's syndrome) and the segmental trisomy Ts65Dn mouse model of Down's syndrome exhibit an increased content of myo-inositol in the brain and cerebrospinal fluid (Berry et al, 1999 ;Huang et al, 1999Huang et al, , 2000Shetty et al, 1995Shetty et al, , 2000. This is considered to be due to a gene-dosage effect on expression and activity of SMIT-1, the gene of which is located on human chromosome 21q22.1 and mouse chromosome 16 and is, thus, present in three copies in the affected individuals (Berry et al, 1995 ;McVeigh et al, 2000). The increased content of myo-inositol in the brain of Ts65Dn mice is reduced by treatment with lithium (Huang et al, 2000), in agreement with downregulation of SMIT by lithium ions.…”

Section: Discussionmentioning

confidence: 62%

Sodium-myo-inositol co-transporter (SMIT-1) mRNA is increased in neutrophils of patients with bipolar 1 disorder and down-regulated under treatment with mood stabilizers

Willmroth

Drieling

Lamla

et al. 2006

Int. J. Neuropsychopharm.

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Recent in-vitro data indicate that depletion of neural cells of myo-inositol by virtue of down-regulation of the high-affinity sodium-myo-inositol co-transporter (SMIT) may be a common mechanism of action of the mood stabilizers lithium, valproate and carbamazepine. The authors sought to investigate whether or not down-regulation of SMIT also occurs in vivo in bipolar patients. Expression of SMIT mRNA was measured in neutrophils of bipolar patients either unmedicated or treated with lithium salts or valproate and in neutrophils of unmedicated, matched healthy controls using quantitative real-time PCR. The content of SMIT mRNA was significantly reduced in neutrophils of lithium-treated bipolar patients compared to controls and to untreated bipolar patients. Untreated bipolar I patients but not bipolar II patients exhibited a significantly higher expression of SMIT mRNA than controls. Neutrophils of bipolar I patients treated with valproate exhibited a significantly lower expression of SMIT mRNA than untreated bipolar I patients but did not differ from controls. These results suggest that lithium and valproate down-regulate SMIT mRNA in vivo in patients. In addition the data provide first evidence that up-regulation of SMIT might be associated with an increased risk for bipolar I disorder.

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Murine chromosome 16 telomeric region, homologous with human chromosome 21q22, contains the osmoregulatory Na<sup>+</sup>/myo-inositol cotransporter (SLC5A3) gene

Cited by 14 publications

References 38 publications

Inositol transport proteins

Inositol transport proteins

Characterization of the Expression and Regulation of Genes Necessary for myo-Inositol Biosynthesis and Transport in the Seminiferous Epithelium1

Sodium-myo-inositol co-transporter (SMIT-1) mRNA is increased in neutrophils of patients with bipolar 1 disorder and down-regulated under treatment with mood stabilizers

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