Details

Autor(en) / Beteiligte

• Porcellati, Francesca
• Hlaing, Tommy
• Togawa, Masaki
• Stevens, Martin J
• Larkin, Dennis D
• Hosaka, Yoshiyuki
• Glover, Thomas W
• Henry, Douglas N
• Greene, Douglas A
• Killen, Paul D

Titel

Human Na + - myo-inositol cotransporter gene: alternate splicing generates diverse transcripts

Ist Teil von

• American Journal of Physiology: Cell Physiology, 1998-05, Vol.274 (5), p.C1215

Ort / Verlag

United States

Erscheinungsjahr

1998

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• Na - myo-inositol cotransport activity generally maintains millimolar intracellular concentrations of myo-inositol and specifically promotes transepithelial myo-inositol transport in kidney, intestine, retina, and choroid plexus. Glucose-induced, tissue-specific myo-inositol depletion and impaired Na - myo-inositol cotransport activity are implicated in the pathogenesis of diabetic complications, a process modeled in vitro in cultured human retinal pigment epithelium (RPE) cells. To explore this process at the molecular level, a human RPE cDNA library was screened with a canine Na -dependent myo-inositol cotransporter (SMIT) cDNA. Overlapping cDNAs spanning 3569 nt were cloned. The resulting cDNA sequence contained a 2154-nt open reading frame, 97% identical to the canine SMIT amino acid sequence. Genomic clones containing SMIT exons suggested that the cDNA is derived from at least five exons. Hypertonic stress induced a time-dependent increase, initially in a 16-kb transcript and subsequently in 11.5-, 9.8-, 8.5-, 3.8-, and ∼1.2-kb SMIT transcripts, that was ascribed to alternate exon splicing using exon-specific probes and direct cDNA sequencing. The human SMIT gene is a complex multiexon transcriptional unit that by alternate exon splicing generates multiple SMIT transcripts that accumulate differentially in response to hypertonic stress.