ArticleMolecular and cellular biology2013
Upregulation of the Rab27a-dependent trafficking and secretory mechanisms improves lysosomal transport, alleviates endoplasmic reticulum stress, and reduces lysosome overload in cystinosis.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 63 citations in OpenAlex.
- Modulating immune toxicity in ulcerative colitis using a small molecule RAB27A inhibitor.Inflammatory bowel diseases · 2026Article
- Cystinosin/Ers1 functions in redox homeostasis in the early secretory pathway.bioRxiv : the preprint server for biology · 2026Article
- From Molecular Understanding and Pathophysiology to Disease Management; A Practical Approach and Guidance to the Management of the Ocular Manifestations of Cystinosis.International journal of molecular sciences · 2025Review
- Lipogenesis and MASLD: re-thinking the role of SREBPs.Archives of toxicology · 2025Review
- Article
- Reconstitution of Rab11-FIP4 Expression Rescues Cellular Homeostasis in Cystinosis.Molecular and cellular biology · 2024Article
- Lysosomes in senescence and aging.EMBO reports · 2023Review
- Dietary supplementation of cystinotic mice by lysine inhibits the megalin pathway and decreases kidney cystine content.Scientific reports · 2023Article
- Article
- Structural basis for proton coupled cystine transport by cystinosin.Nature communications · 2022Article
- Inhibiting SCAP/SREBP exacerbates liver injury and carcinogenesis in murine nonalcoholic steatohepatitis.The Journal of clinical investigation · 2022Article
- DYNC1LI2 regulates localization of the chaperone-mediated autophagy receptor LAMP2A and improves cellular homeostasis in cystinosis.Autophagy · 2022Article
- Review
- Article
- Review
- Cysteamine-bicalutamide combination therapy corrects proximal tubule phenotype in cystinosis.EMBO molecular medicine · 2021Article
- Lysosomal Storage Disorders Shed Light on Lysosomal Dysfunction in Parkinson's Disease.International journal of molecular sciences · 2020Review
- Urinary ERdj3 and mesencephalic astrocyte-derived neutrophic factor identify endoplasmic reticulum stress in glomerular disease.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Occludin protects secretory cells from ER stress by facilitating SNARE-dependent apical protein exocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Regulation of TFEB activity and its potential as a therapeutic target against kidney diseases.Cell death discovery · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Cystinosis is a lysosomal storage disorder caused by the accumulation of the amino acid cystine due to genetic defects in the CTNS gene, which encodes cystinosin, the lysosomal cystine transporter. Although many cellular dysfunctions have been described in cystinosis, the mechanisms leading to these defects are not well understood. Here, we show that increased lysosomal overload induced by accumulated cystine leads to cellular abnormalities, including vesicular transport defects and increased endoplasmic reticulum (ER) stress, and that correction of lysosomal transport improves cellular function in cystinosis. We found that Rab27a was expressed in proximal tubular cells (PTCs) and partially colocalized with the lysosomal marker LAMP-1. The expression of Rab27a but not other small GTPases, including Rab3 and Rab7, was downregulated in kidneys from Ctns-/- mice and in human PTCs from cystinotic patients. Using total internal reflection fluorescence microscopy, we found that lysosomal transport is impaired in Ctns-/- cells. Ctns-/- cells showed significant ER expansion and a marked increase in the unfolded protein response-induced chaperones Grp78 and Grp94. Upregulation of the Rab27a-dependent vesicular trafficking mechanisms rescued the defective lysosomal transport phenotype and reduced ER stress in cystinotic cells. Importantly, reconstitution of lysosomal transport mediated by Rab27a led to decreased lysosomal overload, manifested as reduced cystine cellular content. Our data suggest that upregulation of the Rab27a-dependent lysosomal trafficking and secretory pathways contributes to the correction of some of the cellular defects induced by lysosomal overload in cystinosis, including ER stress.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.