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Dis Model Mech. 2011 January; 4(1): 124.
PMCID: PMC3014353

TRANSLATIONAL IMPACT

Clinical issue

Juvenile Batten disease is the most common neurodegenerative disease of childhood, with an incidence of around 1 in 40,000 live births. Children with the disease start to lose vision at around age 5 and are typically blind by age 7–8. Cognitive and motor decline ensues. Patients typically experience an increasing number of seizures as the disease progresses. Other neurological complications can include schizophrenia, parkinsonism and various behavioral problems. There is no cure and no way of slowing disease progression, and sufferers commonly die blind, demented and bedridden in their late teens or early twenties.

A hallmark of juvenile Batten disease is a lysosomal storage defect characterized by the build-up of lipofuscins (autofluorescent pigment granules composed of lipid-containing residues of lysosomal digestion) in the body’s tissues. In accordance with this, the defective protein in this disease, CLN3, is a lysosomal membrane protein, although other subcellular locations have also been reported. The exact function of CLN3 is unknown.

Results

Human CLN3 can complement the function of the yeast gene Btn1, suggesting that the primordial function of CLN3 is sufficiently conserved to make studies in yeast relevant to the human disease. In this paper, the authors investigate the subcellular localization of Btn1p, and show that its levels and subcellular localization are dependent on the extracellular pH. They go on to demonstrate that Btn1p at different pH values (and thus different subcellular locations) has a different glycosylation pattern, indicating that Btn1p subcellular localization might be determined by this posttranslational modification.

Implications and future directions

These findings suggest that Btn1p functions in different cellular locations in a pH-dependent manner. Btn1p, and by extension CLN3, might therefore play multiple roles in the cell, participating in and regulating different cellular pathways in combination with diverse protein partners. In addition, CLN3 might localize to different subcellular locations in a cell-type-specific manner, providing clues as to why only certain cell types, such as neurons, are affected by the loss of normal CLN3 function.


Articles from Disease Models & Mechanisms are provided here courtesy of Company of Biologists