ArticleHuman molecular genetics2018
Loss of CLN7 results in depletion of soluble lysosomal proteins and impaired mTOR reactivation.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
- Liposomes can directly modulate serine hydrolase activity and lipid metabolism independent of cargo.Chemical science · 2026Article
- Neuronal ceroid lipofuscinosis: underlying mechanisms and emerging therapeutic targets.Nature reviews. Neurology · 2025Review
- CLN7 protein functions at the interface between endolysosomes and stress granules to promote cell survival.Cell death & disease · 2025Article
- Neuronal Ceroid Lipofuscinosis-Concepts, Classification, and Avenues for Therapy.CNS neuroscience & therapeutics · 2025Review
- Pathological Functions of Lysosomal Ion Channels in the Central Nervous System.International journal of molecular sciences · 2024Review
- Modulation of Lysosomal ClCells · 2023Article
- Loss of the batten disease protein CLN3 leads to mis-trafficking of M6PR and defective autophagic-lysosomal reformation.Nature communications · 2023Article
- Converging links between adult-onset neurodegenerative Alzheimer's disease and early life neurodegenerative neuronal ceroid lipofuscinosis?Neural regeneration research · 2023Review
- Article
- KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses.Science advances · 2022Article
- Lysosomal Proteomics Links Disturbances in Lipid Homeostasis and Sphingolipid Metabolism to CLN5 Disease.Cells · 2022Article
- Recent Insight into the Genetic Basis, Clinical Features, and Diagnostic Methods for Neuronal Ceroid Lipofuscinosis.International journal of molecular sciences · 2022Review
- Mass spectrometry-based proteomics in neurodegenerative lysosomal storage disorders.Molecular omics · 2022Review
- Autophagy in the Neuronal Ceroid Lipofuscinoses (Batten Disease).Frontiers in cell and developmental biology · 2022Review
- Article
- Glial Dysfunction and Its Contribution to the Pathogenesis of the Neuronal Ceroid Lipofuscinoses.Frontiers in neurology · 2022Review
- Mfsd8 Modulates Growth and the Early Stages of Multicellular Development inFrontiers in cell and developmental biology · 2022Article
- Altered protein secretion in Batten disease.Disease models & mechanisms · 2021Review
- Repurposing of tamoxifen ameliorates CLN3 and CLN7 disease phenotype.EMBO molecular medicine · 2021Article
- CLN3, at the crossroads of endocytic trafficking.Neuroscience letters · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Defects in the MFSD8 gene encoding the lysosomal membrane protein CLN7 lead to CLN7 disease, a neurodegenerative lysosomal storage disorder belonging to the group of neuronal ceroid lipofuscinoses. Here, we have performed a SILAC-based quantitative analysis of the lysosomal proteome using Cln7-deficient mouse embryonic fibroblasts (MEFs) from a Cln7 knockout (ko) mouse model. From 3335 different proteins identified, we detected 56 soluble lysosomal proteins and 29 highly abundant lysosomal membrane proteins. Quantification revealed that the amounts of 12 different soluble lysosomal proteins were significantly reduced in Cln7 ko MEFs compared with wild-type controls. One of the most significantly depleted lysosomal proteins was Cln5 protein that underlies another distinct neuronal ceroid lipofuscinosis disorder. Expression analyses showed that the mRNA expression, biosynthesis, intracellular sorting and proteolytic processing of Cln5 were not affected, whereas the depletion of mature Cln5 protein was due to increased proteolytic degradation by cysteine proteases in Cln7 ko lysosomes. Considering the similar phenotypes of CLN5 and CLN7 patients, our data suggest that depletion of CLN5 may play an important part in the pathogenesis of CLN7 disease. In addition, we found a defect in the ability of Cln7 ko MEFs to adapt to starvation conditions as shown by impaired mammalian target of rapamycin complex 1 reactivation, reduced autolysosome tubulation and increased perinuclear accumulation of autolysosomes compared with controls. In summary, depletion of multiple soluble lysosomal proteins suggest a critical role of CLN7 for lysosomal function, which may contribute to the pathogenesis and progression of CLN7 disease.
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