CLN3P, the Batten's disease protein, is a novel palmitoyl-protein Delta-9 desaturase.
OBJECTIVE
Batten's disease, one of the most common recessively inherited, untreatable, neurodegenerative diseases of humans, is characterized by progressive neuronal loss and intraneuronal proteolipid storage. Although the gene for the disorder was cloned more than a decade ago, the function of the encoded protein, CLN3P, has not been defined thus far.


METHODS
Sequence analysis using the Pfam server identified a low stringency match to a fatty acid desaturase domain in the N-terminal sequence of CLN3P. We developed a fatty acid desaturase assay based on measurement of desaturase products by gas chromatography/mass spectrometry.


RESULTS
We show that CLN3P is a novel palmitoyl-protein Delta-9 desaturase, which converts membrane-associated palmitoylated proteins to their respective palmitoleated derivatives. We have further demonstrated that this palmitoyl-protein Delta-9 desaturase activity is deficient in cln3(-/-) mouse pancreas and is completely ablated in neuroblastoma cells by RNA inhibition.


CONCLUSIONS
We propose that palmitoyl-protein desaturation defines a new mechanism of proteolipid modification, and that deficiency of this process leads to the signs and symptoms of Batten's disease.
Narayan
Srinivas B
SB
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA.
Rakheja
Dinesh
D
Department of Pathology, Children's Medical Center, Dallas, TX.|Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX.
Tan
Lu
L
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA.
Pastor
Johanne V
JV
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX.
Bennett
Michael J
MJ
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA.|Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA.
D000818:Animals; D015153:Blotting, Western; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D015870:Gene Expression / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism; D009410:Nerve Degeneration / Q000503:physiopathology; D009447:Neuroblastoma / Q000648:ultrastructure; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D013230:Stearoyl-CoA Desaturase / Q000235:genetics* / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000648:ultrastructure
C105199:CLN3 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D013230:Stearoyl-CoA Desaturase