RGD Reference Report - Mouse SGLT3a generates proton-activated currents but does not transport sugar.

General

Mouse SGLT3a generates proton-activated currents but does not transport sugar.
Authors:	Barcelona, S Menegaz, D Diez-Sampedro, A
Citation:	Barcelona S, etal., Am J Physiol Cell Physiol. 2012 Apr 15;302(8):C1073-82. doi: 10.1152/ajpcell.00436.2011. Epub 2012 Feb 1.
RGD ID:	8554112
Pubmed:	PMID:22301059 (View Abstract at PubMed)
DOI:	DOI:10.1152/ajpcell.00436.2011 (Journal Full-text)
Sodium-glucose cotransporters (SGLTs) are secondary active transporters belonging to the SLC5 gene family. SGLT1, a well-characterized member of this family, electrogenically transports glucose and galactose. Human SGLT3 (hSGLT3), despite sharing a high amino acid identity with human SGLT1 (hSGLT1), does not transport sugar, although functions as a sugar sensor. In contrast to humans, two different genes in mice and rats code for two different SGLT3 proteins, SGLT3a and SGLT3b. We previously cloned and characterized mouse SGLT3b (mSGLT3b) and showed that, while it does transport sugar like SGLT1, it likely functions as a physiological sugar sensor like hSGLT3. In this study, we cloned mouse SGLT3a (mSGLT3a) and characterized it by expressing it in Xenopus laevis oocytes and performing electrophysiology and sugar transport assays. mSGLT3a did not transport sugar, and sugars did not induce currents at pH 7.4, though acidic pH induced inward currents that increased in the presence of sugar. Moreover, mutation of residue 457 from glutamate to glutamine resulted in a Na(+)-dependent transport of sugar that was inhibited by phlorizin. To corroborate our results in oocytes, we expressed and characterized mSGLT3a in mammalian cells and confirmed our findings. In addition, we cloned, expressed, and characterized rat SGLT3a in oocytes and found characteristics similar to mSGLT3a. In summary, acidic pH induces currents in mSGLT3a, and sugar-induced currents are increased at acidic pH, but wild-type SGLT3a does not transport sugar.

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Biological Process

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
proton transmembrane transport	acts_upstream_of_or_within	IDA		8554112	PMID:22301059	MGI

Molecular Function

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
proton transmembrane transporter activity	enables	IDA		8554112	PMID:22301059	MGI

Objects Annotated

Genes (Rattus norvegicus)

Slc5a4 (solute carrier family 5 member 4)

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Mouse SGLT3a generates proton-activated currents but does not transport sugar.