Lysosomal Storage of the DCCD Reactive Proteolipid Subunit of Mitochondrial ATP Synthase in Human and Ovine Ceroid Lipofuscinoses

Dn, Palmer; Im, Fearnley; Sm, Medd; Walker, John E.; Rd, Martinus; Sl, Bayliss; Na, Hall; Lake, B D; Ls, Wolfe; Jolly, RD

doi:10.1007/978-1-4899-5339-1_15

Cited by 74 publications

(31 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In all types of NCL that have been characterized to date, the storage bodies have been reported to contain predominantly a single protein or a few major proteins: F 0 subunit c of mitochondrial ATP synthase, vacuolar V 0 ATPase subunit c, or saposins A and D (Palmer et al 1986(Palmer et al , 1989(Palmer et al , 1990(Palmer et al , 1997Tyynela et al 1993Tyynela et al , 1997a. Additional proteins are variably associated with the isolated storage bodies, but these have not been well characterized.…”

Section: Discussionmentioning

confidence: 99%

“…A distinctive feature of the NCLs is that the stored material contains predominantly a single protein or relatively few specific proteins (Haltia 2006;Palmer et al 1986Palmer et al , 1989Palmer et al , 1990Palmer et al , 1997Tyynela et al 1993Tyynela et al , 1997a. There are a number of different forms of human NCL that each result from mutations in one of at least eight different genes (PPT1, CLN2, CLN3, CLN5, CLN6, CLN8, CTSD and MFSD8) (Siintola et al 2006(Siintola et al , 2007Steinfeld et al 2006;Wisniewski et al 2001).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Accumulation of glial fibrillary acidic protein and histone H4 in brain storage bodies of Tibetan terriers with hereditary neuronal ceroid lipofuscinosis

Katz

Sanders

Mooney

et al. 2007

J of Inher Metab Disea

View full text Add to dashboard Cite

Summary The neuronal ceroid lipofuscinoses (NCLs) are inherited neurodegenerative diseases characterized by massive accumulation of autofluorescent storage bodies in neurons and other cells. A late‐onset form of NCL occurs in Tibetan terrier dogs. Gel electrophoretic analyses of isolated storage body proteins from brains of affected dogs indicated that a protein of approximately 50 kDa was consistently prominent and a 16 kDa component was present in some brain storage body preparations. Mass spectral analysis identified the 50 kDa protein as glial fibrillary acidic protein (GFAP), isoform 2. GFAP identification was supported by immunoblot and immunohistochemical analyses. Histone H4 was the major protein in the 16 kDa component. Specific accumulation of GFAP and histone H4 in storage bodies has not been previously reported for any of the NCLs. Tibetan terrier NCL may be the canine correlate of one of the human adult‐onset NCLs for which the genetic bases and storage body compositions have not yet been determined.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Accumulation of glial fibrillary acidic protein and histone H4 in brain storage bodies of Tibetan terriers with hereditary neuronal ceroid lipofuscinosis

Katz

Sanders

Mooney

et al. 2007

J of Inher Metab Disea

View full text Add to dashboard Cite

show abstract

“…Several of the genetically-distinct forms of neuronal ceroid lipofuscinosis, including the lateinfantile form, accumulate a small proteolipid, subunit c of mitochondrial ATP synthase (SCMAS), as a major component of the storage material [20]. Accumulation of SCMAS in control and mutant mouse brain was measured by western blotting and immunodetection (Fig.…”

Section: Lysosomal Storage Is Reduced By Low Levels Of Tppi Activitymentioning

confidence: 99%

Residual levels of tripeptidyl-peptidase I activity dramatically ameliorate disease in late-infantile neuronal ceroid lipofuscinosis

Sleat¹,

El-Banna²,

Sohár³

et al. 2008

Molecular Genetics and Metabolism

View full text Add to dashboard Cite

Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a hereditary neurodegenerative disease of childhood that is caused by mutations in the gene (CLN2) encoding the lysosomal protease tripeptidyl-peptidase I (TPPI). LINCL is fatal and there is no treatment of demonstrated efficacy in affected children but preclinical studies with AAV-mediated gene therapy have demonstrated promise in a mouse model. Here, we have generated mouse CLN2 mutants that express different amounts of TPPI activity to benchmark levels required for therapeutic benefits. Approximately 3% of normal TPPI activity in brain delayed disease onset and doubled lifespan to a median of ~9 months compared to mice expressing ~0.2% of normal levels. Expression of 6% of normal TPPI activity dramatically attenuated disease, with a median lifespan of ~20 months which approaches that of unaffected mice. While the life-span of this hypomorph is shortened, disease is late-onset, less severe and progresses slowly compared to mice expressing lower TPPI levels. For gene therapy and other approaches that restore enzyme activity, these results suggest that 6% of normal TPPI activity throughout the CNS of affected individuals will provide a significant therapeutic benefit but higher levels will be required to cure this disease.

show abstract

“…It is known that the functional motif (ATP synthase c subunit signature) as well as the highly conserved protein sequences occurring across various species of subunit c play a vital role in maintaining the normal mitochondrial physiological function (Palmer et al, 1989;Li et al, 2001). …”

Section: Genomicmentioning

confidence: 99%

cDNA, genomic sequence cloning and overexpression of giant panda (Ailuropoda melanoleuca) mitochondrial ATP synthase ATP5G1

Hou

Hou²,

Ding³

et al. 2012

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. The ATP5G1 gene is one of the three genes that encode mitochondrial ATP synthase subunit c of the proton channel. We cloned the cDNA and determined the genomic sequence of the ATP5G1 gene from the giant panda (Ailuropoda melanoleuca) using RT-PCR technology and touchdown-PCR, respectively. The cloned cDNA fragment contains an open reading frame of 411 bp encoding 136 amino acids; the length of the genomic sequence is of 1838 bp, containing three exons and two introns. Alignment analysis revealed that the nucleotide sequence and the deduced protein sequence are highly conserved compared to Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus, and Sus scrofa. The homologies for nucleotide sequences of the giant panda ATP5G1 to those of these species are 93.92, 92.21, 92.46, 93.67, and 92.46%, respectively, and the homologies for amino acid sequences are 90. 44, 95.59, 93.38, 94.12, and 91.91%, respectively. Topology prediction showed that there is one protein kinase C phosphorylation site, one ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (3): 3164-3174 (2012) ATP5G1 of the giant panda 3165 casein kinase II phosphorylation site, five N-myristoylation sites, and one ATP synthase c subunit signature in the ATP5G1 protein of the giant panda. The cDNA of ATP5G1 was transfected into Escherichia coli, and the ATP5G1 fused with the N-terminally GST-tagged protein gave rise to accumulation of an expected 40-kDa polypeptide, which had the characteristics of the predicted protein.

show abstract

Lysosomal Storage of the DCCD Reactive Proteolipid Subunit of Mitochondrial ATP Synthase in Human and Ovine Ceroid Lipofuscinoses

Cited by 74 publications

References 0 publications

Accumulation of glial fibrillary acidic protein and histone H4 in brain storage bodies of Tibetan terriers with hereditary neuronal ceroid lipofuscinosis

Accumulation of glial fibrillary acidic protein and histone H4 in brain storage bodies of Tibetan terriers with hereditary neuronal ceroid lipofuscinosis

Residual levels of tripeptidyl-peptidase I activity dramatically ameliorate disease in late-infantile neuronal ceroid lipofuscinosis

cDNA, genomic sequence cloning and overexpression of giant panda (Ailuropoda melanoleuca) mitochondrial ATP synthase ATP5G1

Contact Info

Product

Resources

About