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

Research output: Contribution to journalArticle

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 slices and dissociated postnatal primary cultures. Our studies reveal new mechanistic features involved in the pathophysiology of this devastating neurodegenerative disease.

Details

Authors
  • Tamar Sapir
  • Michal Segal
  • Gayane Grigoryan
  • Karin M. Hansson
  • Peter James
  • Menahem Segal
  • Orly Reiner
Organisations
External organisations
  • Weizmann Institute of Science Israel
  • University of Turku
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • Hippocampal neurons, Mass-spectrometry, Palmitoyl-protein thioesterase 1, Palmitoylation, PPT1
Original languageEnglish
Article number92
JournalFrontiers in Cellular Neuroscience
Volume13
Publication statusPublished - 2019 Jan 29
Publication categoryResearch
Peer-reviewedYes