期刊
TRAFFIC
卷 9, 期 11, 页码 1905-1914出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1600-0854.2008.00807.x
关键词
Batten; CLN3; Golgi; mannose 6-phosphate; neuronal ceroid lipofuscinosis; receptor
类别
资金
- Medical Research Council UK
- Children's Brain Diseases Foundation USA
- European Commission [LSHM-CT-2003-503051]
- MRC [MC_U122665003, G0700750] Funding Source: UKRI
- Medical Research Council [G0700750, MC_U122665003] Funding Source: researchfish
The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are a group of inherited childhood-onset neurodegenerative disorders characterized by the lysosomal accumulation of undigested material within cells. To understand this dysfunction, we analysed trafficking of the cation-independent mannose 6-phosphate receptor (CI-MPR), which delivers the digestive enzymes to lysosomes. A common form of NCL is caused by mutations in CLN3, a multipass transmembrane protein of unknown function. We report that ablation of CLN3 causes accumulation of CI-MPR in the trans Golgi network, reflecting a 50% reduction in exit. This CI-MPR trafficking defect is accompanied by a fall in maturation and cellular activity of lysosomal cathepsins. CLN3 is therefore essential for trafficking along the route needed for delivery of lysosomal enzymes, and its loss thereby contributes to and may explain the lysosomal dysfunction underlying Batten disease.
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