Identification of an Alternative Transcript from the Human Iduronate-2-sulfatase (IDS) Gene

Malmgren, Helena; Carlberg, Britt-Marie; Pettersson, Ulf; Bondeson, Marie-Louise

doi:10.1006/geno.1995.1249

Cited by 15 publications

(5 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our findings confirm the results of previous preliminary reports that detected the presence of IDS in several tissues, including pancreatic cells, by differential display and Northern blot analysis (12,24). IDS is a component of lysosomes in fibroblasts (22).…”

Section: Discussionsupporting

confidence: 82%

Identification of iduronate-2-sulfatase in mouse pancreatic islets

Coronado-Pons¹,

Novials²,

Casas³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

The lysosomal enzyme iduronate-2-sulfatase (IDS) is expressed in pancreatic islets and is responsible for degradation of proteoglycans, such as perlecan and dermatan sulfate. To determine the role of IDS in islets, expression and regulation of the gene and localization of the enzyme were investigated in mouse pancreatic islets and clonal cells. The Ids gene was expressed in mouse islets and β- and α-clonal cells, in which it was localized intracellularly in lysosomes. The transcriptional expression of Ids in mouse islets increased with glucose in a dose-dependent manner (11.5, 40.2, 88, and 179% at 5.5, 11.1, 16.7, and 24.4 mM, respectively, P < 0.01 for 16.7 and 24.4 mM glucose vs. 3 mM glucose). This increase was not produced by glyceraldehyde (1 mM) or 6-deoxyglucose (21.4 mM) and was blocked by the addition of mannoheptulose (21.4 mM). Neither insulin content nor secretory response to glucose (16.7 mM) was altered in mouse islets infected with lentiviral constructs carrying the IDS gene in sense orientation. Furthermore, no decrease in islet cell viability was observed in mouse islets carrying lentiviral contracts compared with controls. However, insulin content was reduced (35% vs. controls, P < 0.001) in islets infected with IDS antisense construct, while the secretory response of those islets to glucose was maintained. Inhibition of IDS by antisense infection led to an increase in lysosomal size and a high rate of insulin granule degradation via the crinophagic route in pancreatic β-cells. We conclude that IDS is localized in lysosomes in pancreatic islet cells and expression is regulated by glucose. IDS has a potential role in the normal pathway of lysosomal degradation of secretory peptides and is likely to be essential to maintain pancreatic β-cell function.

show abstract

Section: Discussionsupporting

confidence: 82%

Identification of iduronate-2-sulfatase in mouse pancreatic islets

Coronado-Pons¹,

Novials²,

Casas³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…The lysosomal enzyme IDS has been detected in several tissues, including the pancreas (6,12). Previous findings by our group demonstrated the presence of IDS in mouse pancreatic ␣-and ␤-islet cells (5), which we have now detected for the first time in human pancreatic islets.…”

Section: Discussionsupporting

confidence: 58%

Role of iduronate-2-sulfatase in glucose-stimulated insulin secretion by activation of exocytosis

Piquer¹,

Casas²,

Quesada³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Piquer S, Casas S, Quesada I, Nadal A, Julià M, Novials A, Gomis R. Role of iduronate-2-sulfatase in glucose-stimulated insulin secretion by activation of exocytosis. Am J Physiol Endocrinol Metab 297: E793-E801, 2009. First published July 14, 2009 doi:10.1152/ajpendo.90878.2008.-Iduronate-2-sulfatase (IDS) is a lysosomal enzyme expressed in pancreatic islets responsible for the degradation of proteoglycans such as perlecan and dermatan sulfate. Previous findings of our group demonstrated the involvement of IDS in the normal pathway of lysosomal degradation of secretory peptides, suggesting a role of this enzyme in ␤-cell secretory functionality. The present study was undertaken to characterize the effect of IDS overexpression on insulin release. INS1E cells were transiently transfected with a construct encoding human IDS (hIDS). hIDS overexpression was associated with a gain of function detected by a reduction in heparan sulfate content. hIDS potentiated the glucose-stimulated insulin secretory response compared with controls (61%) with no changes in insulin mRNA levels or insulin peptide content. Results on quantification of the exocytotic process showed a significant increase in hIDS-transfected cells compared with controls. Furthermore, ultramorphological analysis demonstrated an increase in the number of granules in the immediate vicinity of the plasma membrane in hIDStransfected cells and a decrease in total vesicles per square micrometer. hIDS overexpression induced phosphorylation of protein kinase C (PKC) ␣ and its newly myristoylated alanine-rich C kinase substrate, MARCKS. We conclude that IDS has a role in glucose-stimulated insulin secretion via a mechanism that involves the activation of exocytosis through phosphorylation of PKC␣ and MARCKS.

show abstract

“…3 A 1.4-kb alternative transcript that lacks exons 8 and 9 but contains an alternative terminal exon 7 has been reported, although the significance of this alternative form is not well known. 4 At 20 kb telomeric to the IDS locus, there is a predicted locus, LOC727913 (RefSeq XM_001126136), that is highly homologous to part of exon 2, intron 2 and exon 3 of the IDS gene ( Figure 1c). [5][6][7] The IDSP1 locus, which is the only pseudogene of IDS in the human genome, is located B25 kb telomeric to IDS and spans 1.6 kb in an inverse orientation.…”

Section: Introductionmentioning

confidence: 99%

LCR-initiated rearrangements at the IDS locus, completed with Alu-mediated recombination or non-homologous end joining

et al. 2011

View full text Add to dashboard Cite

Mucopolysaccharidosis type II (MPS II) is caused by mutations in the IDS gene, which encodes the lysosomal enzyme iduronate-2-sulfatase. In B20% of MPS II patients the disorder is caused by gross IDS structural rearrangements. We identified two male cases harboring complex rearrangements involving the IDS gene and the nearby pseudogene, IDSP1, which has been annotated as a low-copy repeat (LCR). In both cases the rearrangement included a partial deletion of IDS and an inverted insertion of the neighboring region. In silico analyses revealed the presence of repetitive elements as well as LCRs at the junctions of rearrangements. Our models illustrate two alternative consequences of rearrangements initiated by non-allelic homologous recombination of LCRs: resolution by a second recombination event (that is, Alu-mediated recombination), or resolution by non-homologous end joining repair. These complex rearrangements have the potential to be recurrent and may be present among those MSP II cases with previously uncharacterized aberrations involving IDS.

show abstract

Identification of an Alternative Transcript from the Human Iduronate-2-sulfatase (IDS) Gene

Cited by 15 publications

References 0 publications

Identification of iduronate-2-sulfatase in mouse pancreatic islets

Identification of iduronate-2-sulfatase in mouse pancreatic islets

Role of iduronate-2-sulfatase in glucose-stimulated insulin secretion by activation of exocytosis

LCR-initiated rearrangements at the IDS locus, completed with Alu-mediated recombination or non-homologous end joining

Contact Info

Product

Resources

About