Cystinosis, Nephropathic Proteins (CTNS)

Human Cystinosis, Nephropathic (CTNS) interaction partners

1. Cystinosis was primarily diagnosed by a pediatric nephrologist and then referred to the Iran University of Medical Sciences genetics clinic for consultation and molecular analysis, which involved polymerase chain reaction (PCR) amplification to determine the presence or absence of the 57-kb founder deletion in CTNS, followed by direct sequencing of the coding exons of CTNS

2. Potential dual function of PQ-loop proteins such as cystinosin.

3. To study the role of the cystinosin-LKG-isoform, we have investigated cystine accumulation and apoptosis that have been described in cystinotic cells. The levels of TNFalpha (show TNF Proteins)- and actinomycin D-inducted apoptosis dropped in cystinotic cells expressing LKG-isoform. This effect was also similar to the main isoform.

4. This work demonstrated no major abnormality ofER and lysosomal Ca2 (show CA2 Proteins)+signalling associated with cystinosin defi-ciency in human proximal tubular epithelial cells.

5. The coding exons of the CTNS gene in 5 different Jordanian families and one family from Sudan with nephropathic cystinosis were sequenced. None had the European 57-kb deletion. 7 variants in the coding and promoter sequence of the CTNS gene were found: 294C>T, -180T>C, -118C>T, c.504G>A, p.Thr168Thr, c.829dupA in exon 10, and c.890G>A in exon 11.

6. Results show that the high turnover of ITILELP mutation (del AA67-73) in cystinosin, because of its immature glycosylation state together with low transport activity, might be responsible for the phenotype observed in some cystinosis patients who carry this mutation.

7. silencing of AP-2 (show GTF3A Proteins) triggers the clathrin-independent endocytosis, showing the complex adaptability of cystinosin-LKG trafficking

8. upon comparison of the patients with cystinosis in this particular region with the European and North American patients, it is clear that different CTNS variants result in this disease.

9. GCK (show GCK Proteins) mutations are associated with Cystinosis.

10. Lack of cystinosin reduced TFEB (show TFEB Proteins) expression and induced TFEB (show TFEB Proteins) nuclear translocation.

Mouse (Murine) Cystinosis, Nephropathic (CTNS) interaction partners

1. LAMP2A trafficking is regulated by cystinosin, Rab11, and RILP and that CMA up-regulation is a potential clinically relevant mechanism to increase cell survival in cystinosis.

2. Data indicate that hematopoietic stem cell (HSC (show FUT1 Proteins)) transplantation in cystinosin knockout (Ctns-/-) thyroid drastically decreased cystine accumulation and normalized the thyroid-stimulating hormone level.

3. Cells and tissues lacking CTNS expression are characterized by increased autophagosome numbers, but functional macroautophagic flux.

4. The Ctns(-/-) mouse model generated on C57BL/6 background is not suitable for clarifying the pathogenesis of male infertility in cystinosis.

5. Deletion of cystinosis gene (Ctns) causes corneal cystine crystals formation, neovascularization and scarring in the cornea of ctns transgenic mice mimicking cystinosis in humans.

6. the cause of cellular ATP depletion in nephrotic cystinosis may be the futile cycle (show LRMP Proteins), formed between two ATP-dependant gamma-glutamyl cycle enzymes, gamma-glutamyl cysteine synthetase and 5-oxoprolinase (show OPLAH Proteins)

7. CTNS has a role in proper functioning of the retina and bones, and in mouse behavior

8. Temporospatial pattern of cystine accumulation in Ctns-/- mice parallels that of patients and validates the mice as a model for the ocular anomalies of cystinosis.