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First published online 12 August 2008
doi: 10.1242/jcs.030122
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Research Article |
1 MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT
2 Department of Genetics, Evolution and Environment, University College London, Gower Street, London WC1E 6BT
3 MRC Cell Biology Unit, Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT
4 General and Adolescent Paediatric Unit, UCL Institute of Child Health, University College London, Gower Street, London WC1E 6BT
* Author for correspondence (e-mail: s.mole{at}ucl.ac.uk)
Accepted 12 June 2008
btn1, the Schizosaccharomyces pombe orthologue of the human Batten-disease gene CLN3, is involved in vacuole pH homeostasis. We show that loss of btn1 also results in a defective cell wall marked by sensitivity to zymolyase, a β-glucanase. The defect can be rescued by expression of Btn1p or CLN3, and the extent of the defect correlates with disease severity. The vacuole and cell-wall defects are linked by a common pH-dependent mechanism, because they are suppressed by growth in acidic pH and a similar glucan defect is also apparent in the V-type H+ ATPase (v-ATPase) mutants vma1
and vma3
. Significantly, Btn1p acts as a multicopy suppressor of the cell-wall and other vacuole-related defects of these v-ATPase-null cells. In addition, Btn1p is required in a second, pH-independent, process that affects sites of polarised growth and of cell-wall deposition, particularly at the septum, causing cytokinesis problems under normal growth conditions and eventual cell lysis at 37°C. Thus, Btn1p impacts two independent processes, which suggests that Batten disease is more than a pH-related lysosome disorder.
Key words: CLN3, btn1, Batten disease, Neuronal ceroid lipofuscinosis, V-type H+ ATPase (v-ATPase), vma1, vma3, Vacuole, Neurodegeneration, Schizosaccharomyces pombe
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