AUTHOR=Sapir Tamar , Segal Michal , Grigoryan Gayane , Hansson Karin M. , James Peter , Segal Menahem , Reiner Orly 

TITLE=The Interactome of Palmitoyl-Protein Thioesterase 1 (PPT1) Affects Neuronal Morphology and Function

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=13

YEAR=2019

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2019.00092

DOI=10.3389/fncel.2019.00092

ISSN=1662-5102

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 <italic>Ppt1−/−</italic> 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>