A novel role of the Batten disease gene CLN3: association with BMP synthesis.
Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) results from a deficiency of CLN3, a protein recently identified within detergent-resistant membranes (DRMs). To study the function of CLN3 within these domains we isolated DRMs from control and JNCL-brain and noted that JNCL-derived DRMs are less buoyant than control. Analysis of DRM phospholipids derived from JNCL-brain revealed a reduction of bis(monoacylglycerol)phosphate. Metabolic labeling of JNCL-fibroblasts demonstrated a reduction in the synthesis of bis(monoacylglycerol)phosphate which was restored following complementation with wild-type-CLN3, substantiating our initial observation in brain. Metabolic labeling of cell lines overexpressing wild-type-CLN3 resulted in increased bis(monoacylglycerol)phosphate synthesis, while overexpression of mutant CLN3-L170P decreased bis(monoacylglycerol)phosphate synthesis. These data illustrate a new finding, a strong correlation between CLN3 protein expression and synthesis of bis(monoacylglycerol)phosphate.
Hobert
Judith A
JA
Committee on Molecular Metabolism and Nutrition, Biological Sciences Division, The University of Chicago, Chicago, IL, USA. hobertj@ccf.org
Dawson
Glyn
G
D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008246:Lysophospholipids / Q000096:biosynthesis*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D050178:Monoglycerides / Q000096:biosynthesis*; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000378:metabolism*
C105199:CLN3 protein, human; D008246:Lysophospholipids; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D050178:Monoglycerides; C012786:bis(monoacylglyceryl)phosphate