Codlin, S; Haines, RL; Burden, JJE; Mole, SE; (2008) btn1 affects cytokinesis and cell-wall deposition by independent mechanisms, one of which is linked to dysregulation of vacuole pH. J CELL SCI , 121 (17) 2860 - 2870. 10.1242/jcs.030122.
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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 vma1 Delta and vma3 Delta. 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.
|Title:||btn1 affects cytokinesis and cell-wall deposition by independent mechanisms, one of which is linked to dysregulation of vacuole pH|
|Keywords:||CLN3, btn1, Batten disease, neuronal ceroid, lipofuscinosis, V-type H+ ATPase (v-ATPase), vma1, vma3, vacuole, neurodegeneration, Schizosaccharomyces pombe, NEURONAL CEROID-LIPOFUSCINOSIS, LYSOSOMAL STORAGE DISEASE, ALPHA-GLUCAN SYNTHASE, SCHIZOSACCHAROMYCES-POMBE, BATTEN-DISEASE, SACCHAROMYCES-CEREVISIAE, FISSION YEAST, EXOCYTIC PATHWAY, POLARIZED GROWTH, CLN3 PROTEIN|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Genetics, Evolution and Environment|
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