| http://purl.uniprot.org/citations/31025705 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31025705 | http://www.w3.org/2000/01/rdf-schema#comment | "Mutations in at least 13 different genes (called CLNs) underlie various forms of neuronal ceroid lipofuscinoses (NCLs), a group of the most common neurodegenerative lysosomal storage diseases. While inactivating mutations in the CLN1 gene, encoding palmitoyl-protein thioesterases-1 (PPT1), cause infantile NCL (INCL), those in the CLN3 gene, encoding a protein of unknown function, underlie juvenile NCL (JNCL). PPT1 depalmitoylates S-palmitoylated proteins (constituents of ceroid) required for their degradation by lysosomal hydrolases and PPT1-deficiency causes lysosomal accumulation of autofluorescent ceroid leading to INCL. Because intracellular accumulation of ceroid is a characteristic of all NCLs, a common pathogenic link for these diseases has been suggested. It has been reported that CLN3-mutations suppress the exit of cation-independent mannose 6-phosphate receptor (CI-M6PR) from the trans Golgi network (TGN). Because CI-M6PR transports soluble proteins such as PPT1 from the TGN to the lysosome, we hypothesized that CLN3-mutations may cause lysosomal PPT1-insufficiency contributing to JNCL pathogenesis. Here, we report that the lysosomes in Cln3-mutant mice, which mimic JNCL, and those in cultured cells from JNCL patients, contain significantly reduced levels of Ppt1-protein and Ppt1-enzyme activity and progressively accumulate autofluorescent ceroid. Furthermore, in JNCL fibroblasts the V0a1 subunit of v-ATPase, which regulates lysosomal acidification, is mislocalized to the plasma membrane instead of its normal location on lysosomal membrane. This defect dysregulates lysosomal acidification, as we previously reported in Cln1 -/- mice, which mimic INCL. Our findings uncover a previously unrecognized role of CLN3 in lysosomal homeostasis and suggest that CLN3-mutations causing lysosomal Ppt1-insuffiiciency may at least in part contribute to JNCL pathogenesis."xsd:string |
| http://purl.uniprot.org/citations/31025705 | http://purl.org/dc/terms/identifier | "doi:10.1002/jimd.12106"xsd:string |
| http://purl.uniprot.org/citations/31025705 | http://purl.uniprot.org/core/author | "Mondal A."xsd:string |
| http://purl.uniprot.org/citations/31025705 | http://purl.uniprot.org/core/author | "Mukherjee A.B."xsd:string |
| http://purl.uniprot.org/citations/31025705 | http://purl.uniprot.org/core/author | "Sadhukhan T."xsd:string |
| http://purl.uniprot.org/citations/31025705 | http://purl.uniprot.org/core/author | "Casey S."xsd:string |
| http://purl.uniprot.org/citations/31025705 | http://purl.uniprot.org/core/author | "Bagh M.B."xsd:string |
| http://purl.uniprot.org/citations/31025705 | http://purl.uniprot.org/core/author | "Appu A.P."xsd:string |
| http://purl.uniprot.org/citations/31025705 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/31025705 | http://purl.uniprot.org/core/name | "J Inherit Metab Dis"xsd:string |
| http://purl.uniprot.org/citations/31025705 | http://purl.uniprot.org/core/pages | "944-954"xsd:string |
| http://purl.uniprot.org/citations/31025705 | http://purl.uniprot.org/core/title | "Cln3-mutations underlying juvenile neuronal ceroid lipofuscinosis cause significantly reduced levels of Palmitoyl-protein thioesterases-1 (Ppt1)-protein and Ppt1-enzyme activity in the lysosome."xsd:string |
| http://purl.uniprot.org/citations/31025705 | http://purl.uniprot.org/core/volume | "42"xsd:string |
| http://purl.uniprot.org/citations/31025705 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/31025705 |
| http://purl.uniprot.org/citations/31025705 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/31025705 |
| http://purl.uniprot.org/uniprot/#_D3YVA8-mappedCitation-31025705 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31025705 |
| http://purl.uniprot.org/uniprot/#_B4DFF3-mappedCitation-31025705 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31025705 |
| http://purl.uniprot.org/uniprot/#_B4DFT5-mappedCitation-31025705 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31025705 |
| http://purl.uniprot.org/uniprot/#_A8JYI8-mappedCitation-31025705 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31025705 |
| http://purl.uniprot.org/uniprot/#_A8JYI9-mappedCitation-31025705 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31025705 |
| http://purl.uniprot.org/uniprot/#_B4DIA8-mappedCitation-31025705 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31025705 |
| http://purl.uniprot.org/uniprot/#_B4DMY6-mappedCitation-31025705 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31025705 |
| http://purl.uniprot.org/uniprot/#_B4DXV0-mappedCitation-31025705 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31025705 |
| http://purl.uniprot.org/uniprot/#_D3YUU4-mappedCitation-31025705 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31025705 |