Intracellular trafficking of CLN3, the protein underlying the childhood neurodegenerative disease, Batten disease

FEBS Letters

Xia, Haibin¹  Mao, Qinwen¹  Davidson, Beverly L¹ 

[1] Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242, USA

关键词: Batten disease;    Protein trafficking;    CLN3;    Neuronal ceroid lipofuscinose;   

DOI  :  10.1016/S0014-5793(03)01274-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Juvenile neuronal ceroid lipofuscinoses (Batten disease) is a progressive neurodegenerative disorder resulting from mutations in the CLN3 gene, which encodes a hydrophobic 438 amino acid protein of unknown function. Prior studies have shown that CLN3 is expressed in multiple tissues, with highest levels in brain and testis. Experiments using cells overexpressing CLN3 indicate that CLN3 is a lysosomal resident protein. However, studies to date have not addressed trafficking of endogenous CLN3. As such, the purpose of the present study was two-fold. First, to develop a culture model to allow evaluation of native CLN3 transport. Second, to utilize available epitope-specific antibodies to determine if CLN3 reaches the plasma membrane en route to the lysosome. Our data using a NCCIT (embryonic testicular carcinoma) cell model coupled with surface biotinylation and antibody trapping demonstrated that at least a proportion of CLN3 trafficks to the lysosome via the cell membrane. Moreover, inhibition of the μ3A subunit of the AP-3 adapter protein complex increased levels of CLN3 at the cell surface.

【 授权许可】

Unknown