The Interactome of Palmitoyl-Protein Thioesterase 1 (PPT1) Affects Neuronal Morphology and Function
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-bin...
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doaj-6eeddc2e21c24a2f98153361ea4cc5a72020-11-24T21:16:17ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022019-03-011310.3389/fncel.2019.00092427125The Interactome of Palmitoyl-Protein Thioesterase 1 (PPT1) Affects Neuronal Morphology and FunctionTamar Sapir0Michal Segal1Gayane Grigoryan2Karin M. Hansson3Peter James4Peter James5Menahem Segal6Orly Reiner7Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, IsraelDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, IsraelDepartment of Neurobiology, Weizmann Institute of Science, Rehovot, IsraelDepartment of Immunotechnology, Lund University, Lund, SwedenDepartment of Immunotechnology, Lund University, Lund, SwedenTurku Centre for Biotechnology (BTK), University of Turku, Turku, FinlandDepartment of Neurobiology, Weizmann Institute of Science, Rehovot, IsraelDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, IsraelPalmitoyl-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.https://www.frontiersin.org/article/10.3389/fncel.2019.00092/fullpalmitoyl-protein thioesterase 1PPT1hippocampal neuronsmass-spectrometrypalmitoylation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tamar Sapir Michal Segal Gayane Grigoryan Karin M. Hansson Peter James Peter James Menahem Segal Orly Reiner |
spellingShingle |
Tamar Sapir Michal Segal Gayane Grigoryan Karin M. Hansson Peter James Peter James Menahem Segal Orly Reiner The Interactome of Palmitoyl-Protein Thioesterase 1 (PPT1) Affects Neuronal Morphology and Function Frontiers in Cellular Neuroscience palmitoyl-protein thioesterase 1 PPT1 hippocampal neurons mass-spectrometry palmitoylation |
author_facet |
Tamar Sapir Michal Segal Gayane Grigoryan Karin M. Hansson Peter James Peter James Menahem Segal Orly Reiner |
author_sort |
Tamar Sapir |
title |
The Interactome of Palmitoyl-Protein Thioesterase 1 (PPT1) Affects Neuronal Morphology and Function |
title_short |
The Interactome of Palmitoyl-Protein Thioesterase 1 (PPT1) Affects Neuronal Morphology and Function |
title_full |
The Interactome of Palmitoyl-Protein Thioesterase 1 (PPT1) Affects Neuronal Morphology and Function |
title_fullStr |
The Interactome of Palmitoyl-Protein Thioesterase 1 (PPT1) Affects Neuronal Morphology and Function |
title_full_unstemmed |
The Interactome of Palmitoyl-Protein Thioesterase 1 (PPT1) Affects Neuronal Morphology and Function |
title_sort |
interactome of palmitoyl-protein thioesterase 1 (ppt1) affects neuronal morphology and function |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular Neuroscience |
issn |
1662-5102 |
publishDate |
2019-03-01 |
description |
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. |
topic |
palmitoyl-protein thioesterase 1 PPT1 hippocampal neurons mass-spectrometry palmitoylation |
url |
https://www.frontiersin.org/article/10.3389/fncel.2019.00092/full |
work_keys_str_mv |
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