First published online November 23, 2005
Journal of Cell Science 118, 2301e (2005)
© The Company of Biologists Limited
Batten for yeast disease model
Neuronal ceroid lipofuscinoses (NCLs) - or Batten disease - represent a group of fatal inherited neurodegenerative conditions characterized by defects in lysosomal storage. Juvenile-onset NCL (JNCL) is caused by mutations in CLN3. The gene product is thought to be a transmembrane protein present on endosomes and lysosomes; however, its function is unknown. Sara Mole and co-workers have now identified and characterized the fission yeast CLN3 orthologue, Btn1p, shedding new light on its mammalian relative (see p. 5525). They find that yeast lacking Btn1p have specific defects in their vacuoles (equivalent to lysosomes in mammals): these are enlarged and more alkaline than usual. By contrast, vacuoles from yeast overexpressing Btn1p are smaller and more acidic. The authors demonstrate that mutations in Btn1p at positions equivalent to JNCL-causing CLN3 mutations lead to changes in vacuolar pH that correlate with the severity of the disease the CLN3 mutations produce. Moreover, they show that CLN3 can partially compensate for loss of Btn1p in yeast and that the proteins traffic to the same compartments. Mole and co-workers conclude that Btn1p regulates vacuole homeostasis in yeast and propose that this genetically tractable organism will prove a useful model system for further research into JNCL.
Related articles in JCS:
- btn1, the Schizosaccharomyces pombe homologue of the human Batten disease gene CLN3, regulates vacuole homeostasis
- Yannick Gachet, Sandra Codlin, Jeremy S. Hyams, and Sara E. Mole
JCS 2005 118: 5525-5536.
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