ArticleDisease models & mechanisms2015
Partial genetic suppression of a loss-of-function mutant of the neuronal ceroid lipofuscinosis-associated protease TPP1 in Dictyostelium discoideum.
Article in Disease models & mechanisms, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Assaying Lysosomal Enzyme Activity in Dictyostelium discoideum.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Review
- Mfsd8 Modulates Growth and the Early Stages of Multicellular Development inFrontiers in cell and developmental biology · 2022Article
- TheFrontiers in cell and developmental biology · 2022Article
- Autophagy in the Neuronal Ceroid Lipofuscinoses (Batten Disease).Frontiers in cell and developmental biology · 2022Review
- Altered protein secretion in Batten disease.Disease models & mechanisms · 2021Review
- Aberrant Autophagy Impacts Growth and Multicellular Development in aFrontiers in cell and developmental biology · 2021Article
- Review
- Dictyostelium discoideum as a non-mammalian biomedical model.Microbial biotechnology · 2021Review
- Cellular models of Batten disease.Biochimica et biophysica acta. Molecular basis of disease · 2020Review
- Molecular networking in the neuronal ceroid lipofuscinoses: insights from mammalian models and the social amoeba Dictyostelium discoideum.Journal of biomedical science · 2020Review
- Changing Times for CLN2 Disease: The Era of Enzyme Replacement Therapy.Therapeutics and clinical risk management · 2020Review
- Mutation update: Review of TPP1 gene variants associated with neuronal ceroid lipofuscinosis CLN2 disease.Human mutation · 2019Article
- Actin Waves and Dynamic Patterning of the Plasma Membrane.The Yale journal of biology and medicine · 2019Article
- Article
- Review
- Aberrant adhesion impacts early development in a Dictyostelium model for juvenile neuronal ceroid lipofuscinosis.Cell adhesion & migration · 2017Article
- A tripeptidyl peptidase 1 is a binding partner of the Golgi pH regulator (GPHR) inDisease models & mechanisms · 2017Article
- Using the social amoeba Dictyostelium to study the functions of proteins linked to neuronal ceroid lipofuscinosis.Journal of biomedical science · 2016Review
- A canine model for neuronal ceroid lipofuscinosis highlights the promise of gene therapy for lysosomal storage diseases.Annals of translational medicine · 2016Article
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2 authors at 1 institution in 1 country.
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Abstract
Neuronal ceroid lipofuscinosis (NCL) is the most common childhood-onset neurodegenerative disease. NCL is inevitably fatal, and there is currently no treatment available. Children with NCL show a progressive decline in movement, vision and mental abilities, and an accumulation of autofluorescent deposits in neurons and other cell types. Late-infantile NCL is caused by mutations in the lysosomal protease tripeptidyl peptidase 1 (TPP1). TPP1 cleaves tripeptides from the N-terminus of proteins in vitro, but little is known about the physiological function of TPP1. TPP1 shows wide conservation in vertebrates but it is not found in Drosophila, Caenorhabditis elegans or Saccharomyces cerevisiae. Here, we characterize ddTpp1, a TPP1 ortholog present in the social amoeba Dictyostelium discoideum. Lysates from cells lacking ddTpp1 show a reduced but not abolished ability to cleave a TPP1 substrate, suggesting that other Dictyostelium enzymes can perform this cleavage. ddTpp1 and human TPP1 localize to the lysosome in Dictyostelium, indicating conserved function and trafficking. Cells that lack ddTpp1 show precocious multicellular development and a reduced ability to form spores during development. When cultured in autophagy-stimulating conditions, cells lacking ddTpp1 rapidly decrease in size and are less viable than wild-type cells, suggesting that one function of ddTpp1 could be to limit autophagy. Cells that lack ddTpp1 exhibit strongly impaired development in the presence of the lysosome-perturbing drug chloroquine, and this phenotype can be suppressed through a secondary mutation in the gene that we name suppressor of tpp1(-) A (stpA), which encodes a protein with some similarity to mammalian oxysterol-binding proteins (OSBPs). Taken together, these results suggest that targeting specific proteins could be a viable way to suppress the effects of loss of TPP1 function.
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