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The interactome of palmitoyl-protein thioesterase 1 (PPT1) affects neuronal morphology and function

Sapir, Tamar; Segal, Michal; Grigoryan, Gayane; Hansson, Karin M. LU ; James, Peter LU ; Segal, Menahem and Reiner, Orly (2019) In Frontiers in Cellular Neuroscience 13.
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Hippocampal neurons, Mass-spectrometry, Palmitoyl-protein thioesterase 1, Palmitoylation, PPT1
in
Frontiers in Cellular Neuroscience
volume
13
publisher
Frontiers
external identifiers
  • scopus:85064197004
ISSN
1662-5102
DOI
10.3389/fncel.2019.00092
language
English
LU publication?
yes
id
817e1822-e20e-4ea8-ba76-07a6bb3c6a35
date added to LUP
2019-05-02 12:03:12
date last changed
2019-05-14 04:55:15
@article{817e1822-e20e-4ea8-ba76-07a6bb3c6a35,
  abstract     = {<p>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.</p>},
  articleno    = {92},
  author       = {Sapir, Tamar and Segal, Michal and Grigoryan, Gayane and Hansson, Karin M. and James, Peter and Segal, Menahem and Reiner, Orly},
  issn         = {1662-5102},
  keyword      = {Hippocampal neurons,Mass-spectrometry,Palmitoyl-protein thioesterase 1,Palmitoylation,PPT1},
  language     = {eng},
  month        = {01},
  publisher    = {Frontiers},
  series       = {Frontiers in Cellular Neuroscience},
  title        = {The interactome of palmitoyl-protein thioesterase 1 (PPT1) affects neuronal morphology and function},
  url          = {http://dx.doi.org/10.3389/fncel.2019.00092},
  volume       = {13},
  year         = {2019},
}