Document Detail

Btn1 affects cytokinesis and cell-wall deposition by independent mechanisms, one of which is linked to dysregulation of vacuole pH.
MedLine Citation:
PMID:  18697832     Owner:  NLM     Status:  MEDLINE    
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 beta-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 vma1Delta and vma3Delta. 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 degrees C. Thus, Btn1p impacts two independent processes, which suggests that Batten disease is more than a pH-related lysosome disorder.
Sandra Codlin; Rebecca L Haines; J Jemima E Burden; Sara E Mole
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-08-12
Journal Detail:
Title:  Journal of cell science     Volume:  121     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-21     Completed Date:  2008-10-30     Revised Date:  2009-02-10    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  2860-70     Citation Subset:  IM    
MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT.
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MeSH Terms
Cell Wall / drug effects,  metabolism*
Cytokinesis* / drug effects
Endocytosis / drug effects
Gene Deletion
Genes, Suppressor
Hydrogen-Ion Concentration / drug effects
Hydrolases / pharmacology
Membrane Proteins / metabolism*
Neuronal Ceroid-Lipofuscinoses / metabolism
Schizosaccharomyces / cytology*,  genetics,  metabolism*,  ultrastructure
Schizosaccharomyces pombe Proteins / metabolism*
Vacuolar Proton-Translocating ATPases / metabolism
Vacuoles / drug effects,  enzymology,  metabolism*
Grant Support
//Medical Research Council; //Wellcome Trust
Reg. No./Substance:
0/BTN1 protein, S pombe; 0/Membrane Proteins; 0/Schizosaccharomyces pombe Proteins; 37340-57-1/zymolyase; EC 3.-/Hydrolases; EC 3.6.1.-/Vacuolar Proton-Translocating ATPases

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