Peter James
Professor
The interactome of palmitoyl-protein thioesterase 1 (PPT1) affects neuronal morphology and function
Author
Summary, in English
Palmitoyl-protein thioesterase 1 (PPT1) is a depalmitoylation enzyme that is mutated in cases of neuronal ceroid lipofuscinosis (NCL). The hallmarks of the disease include progressive neurodegeneration and blindness, as well as seizures. In the current study, we identified 62 high-confident PPT1-binding proteins. These proteins included a self-interaction of PPT1, two V-type ATPases, calcium voltage-gated channels, cytoskeletal proteins and others. Pathway analysis suggested their involvement in seizures and neuronal morphology. We then proceeded to demonstrate that hippocampal neurons from Ppt1−/− mice exhibit structural deficits, and further investigated electrophysiology parameters in the hippocampi of mutant mice, both in brain slices and dissociated postnatal primary cultures. Our studies reveal new mechanistic features involved in the pathophysiology of this devastating neurodegenerative disease.
Department/s
- Department of Immunotechnology
Publishing year
2019-01-29
Language
English
Publication/Series
Frontiers in Cellular Neuroscience
Volume
13
Document type
Journal article
Publisher
Frontiers Media S. A.
Topic
- Neurosciences
Keywords
- Hippocampal neurons
- Mass-spectrometry
- Palmitoyl-protein thioesterase 1
- Palmitoylation
- PPT1
Status
Published
ISBN/ISSN/Other
- ISSN: 1662-5102