Characterizing pathogenic processes in Batten disease: Use of small eukaryotic model systems

Phillips, Seasson N.; Muzaffar, Neda E.; Codlin, Sandra; Korey, Christopher A.; Taschner, Peter E.M.; Voer, Gert de; Mole, Sara; Pearce, David A.

doi:10.1016/j.bbadis.2006.08.010

Cited by 28 publications

(26 citation statements)

References 124 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…An advantage of Drosophila and other small eukaryotic model systems lies in the ability to perform large-scale second-site genetic modifier screens (Muquit and Feany 2002;Phillips et al 2006). This approach allows for the unbiased identification of specific genes and cellular pathways that are relevant to protein function and disease progression.…”

Section: Work In Cultured Ppt1mentioning

confidence: 99%

Genetic Modifiers of Drosophila Palmitoyl–Protein Thioesterase 1-Induced Degeneration

Buff¹,

Smith²,

Korey

2007

Genetics

View full text Add to dashboard Cite

Infantile neuronal ceroid lipofuscinosis (INCL) is a pediatric neurodegenerative disease caused by mutations in the human CLN1 gene. CLN1 encodes palmitoyl-protein thioesterase 1 (PPT1), suggesting an important role for the regulation of palmitoylation in normal neuronal function. To further elucidate Ppt1 function, we performed a gain-of-function modifier screen in Drosophila using a collection of enhancerpromoter transgenic lines to suppress or enhance the degeneration produced by overexpression of Ppt1 in the adult visual system. Modifier genes identified in our screen connect Ppt1 function to synaptic vesicle cycling, endo-lysosomal trafficking, synaptic development, and activity-dependent remodeling of the synapse. Furthermore, several homologs of the modifying genes are known to be regulated by palmitoylation in other systems and may be in vivo substrates for Ppt1. Our results complement recent work on mouse Ppt1À/À cells that shows a reduction in synaptic vesicle pools in primary neuronal cultures and defects in endosomal trafficking in human fibroblasts. The pathways and processes implicated by our modifier loci shed light on the normal cellular function of Ppt1. A greater understanding of Ppt1 function in these cellular processes will provide valuable insight into the molecular etiology of the neuronal dysfunction underlying the disease.

show abstract

Section: Work In Cultured Ppt1mentioning

confidence: 99%

Genetic Modifiers of Drosophila Palmitoyl–Protein Thioesterase 1-Induced Degeneration

Buff¹,

Smith²,

Korey

2007

Genetics

View full text Add to dashboard Cite

show abstract

“…Both Btn1 and Cln3 traffic to the vacuole membrane via early endocytic and pre-vacuolar compartments and localization of Btn1 to the vacuole membrane is dependent on the Ras GTPase Ypt7. Importantly, vacuoles in cells deleted for both YPT7 and BTN1 were larger and more alkaline than those of cells deleted for YPT7 alone, indicating that Btn1 has a functional role prior to reaching the vacuole (Gachet et al, 2005;Phillips et al, 2006).…”

Section: Budding Yeast As a Model To Investigate Prion Functionmentioning

confidence: 95%

Yeast buddies helping to unravel the complexity of neurodegenerative disorders

Fruhmann

Seynnaeve

Zheng

et al. 2017

Mechanisms of Ageing and Development

View full text Add to dashboard Cite

“…Similarly, existence of CLN3P homologs in Caenorhabditis elegans and Drosophila melanogaster make them useful model systems for studying CLN3P biology. The use of small eukaryotic models in characterizing the pathogenic processes in neuronal ceroid-lipofuscinoses has been reviewed recently [84]. Increased acidification of lysosomes and reduced v-ATPase activity has suggested a role for Btn1p and CLN3P in maintaining pH homeostasis [85][86][87][88][89][90][91][92].…”

Section: Function Of Cln3pmentioning

confidence: 99%

Juvenile Neuronal Ceroid-Lipofuscinosis (Batten Disease): A Brief Review and Update

Rakheja¹,

Narayan²,

Bennett³

2007

CMM

View full text Add to dashboard Cite

Juvenile neuronal ceroid-lipofuscinosis (JNCL, Batten disease, Spielmeyer-Vogt-Sjogren disease, CLN3) is the most common inherited, autosomal recessive, neurodegenerative disorder in man. Like the other neuronal ceroid-lipofuscinoses, it is characterized by progressive loss of vision, seizures, and loss of cognitive and motor functions, leading to premature demise. JNCL is caused by mutations of CLN3, a gene that encodes a hydrophobic transmembrane protein, which localizes to membrane lipid rafts in lysosomes, endosomes, synaptosomes, and cell membrane. While the primary function of the CLN3 protein (CLN3P) may be debated, its absence affects numerous cellular functions including pH regulation, arginine transport, membrane trafficking, and apoptosis. We have recently suggested that the unifying primary function of CLN3P may be in a novel palmitoyl-protein Delta-9 desaturase (PPD) activity that in our opinion could explain all of the various functional abnormalities seen in the JNCL cells. Another group of researchers has recently shown a correlation between the CLN3P expression and the synthesis of bis(monoacylglycerol)phosphate (BMP) and suggested that CLN3P may play a role in the biosynthesis of BMP. In this review, following an introduction to the neuronal ceroid-lipofuscinoses, we provide a brief overview and an update of the most recent research in JNCL, specifically that related to the function of CLN3P.

show abstract

Characterizing pathogenic processes in Batten disease: Use of small eukaryotic model systems

Cited by 28 publications

References 124 publications

Genetic Modifiers of Drosophila Palmitoyl–Protein Thioesterase 1-Induced Degeneration

Genetic Modifiers of Drosophila Palmitoyl–Protein Thioesterase 1-Induced Degeneration

Yeast buddies helping to unravel the complexity of neurodegenerative disorders

Juvenile Neuronal Ceroid-Lipofuscinosis (Batten Disease): A Brief Review and Update

Contact Info

Product

Resources

About