PMID- 31555119 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1663-3563 (Print) IS - 1663-3563 (Electronic) IS - 1663-3563 (Linking) VI - 11 DP - 2019 TI - Depalmitoylation by Palmitoyl-Protein Thioesterase 1 in Neuronal Health and Degeneration. PG - 25 LID - 10.3389/fnsyn.2019.00025 [doi] LID - 25 AB - Protein palmitoylation is the post-translational, reversible addition of a 16-carbon fatty acid, palmitate, to proteins. Protein palmitoylation has recently garnered much attention, as it robustly modifies the localization and function of canonical signaling molecules and receptors. Protein depalmitoylation, on the other hand, is the process by which palmitic acid is removed from modified proteins and contributes, therefore, comparably to palmitoylated-protein dynamics. Palmitoylated proteins also require depalmitoylation prior to lysosomal degradation, demonstrating the significance of this process in protein sorting and turnover. Palmitoylation and depalmitoylation serve as particularly crucial regulators of protein function in neurons, where a specialized molecular architecture and cholesterol-rich membrane microdomains contribute to synaptic transmission. Three classes of depalmitoylating enzymes are currently recognized, the acyl protein thioesterases, alpha/beta hydrolase domain-containing 17 proteins (ABHD17s), and the palmitoyl-protein thioesterases (PPTs). However, a clear picture of depalmitoylation has not yet emerged, in part because the enzyme-substrate relationships and specific functions of depalmitoylation are only beginning to be uncovered. Further, despite the finding that loss-of-function mutations affecting palmitoyl-protein thioesterase 1 (PPT1) function cause a severe pediatric neurodegenerative disease, the role of PPT1 as a depalmitoylase has attracted relatively little attention. Understanding the role of depalmitoylation by PPT1 in neuronal function is a fertile area for ongoing basic science and translational research that may have broader therapeutic implications for neurodegeneration. Here, we will briefly introduce the rapidly growing field surrounding protein palmitoylation and depalmitoylation, then will focus on the role of PPT1 in development, health, and neurological disease. FAU - Koster, Kevin P AU - Koster KP AD - Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, United States. FAU - Yoshii, Akira AU - Yoshii A AD - Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, United States. AD - Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, United States. AD - Department of Neurology, University of Illinois at Chicago, Chicago, IL, United States. LA - eng PT - Journal Article PT - Review DEP - 20190829 PL - Switzerland TA - Front Synaptic Neurosci JT - Frontiers in synaptic neuroscience JID - 101548972 PMC - PMC6727029 OTO - NOTNLM OT - NMDA OT - PPT1 OT - depalmitoylation OT - lipofuscinosis OT - neurodegeneration OT - palmitoylation EDAT- 2019/09/27 06:00 MHDA- 2019/09/27 06:01 PMCR- 2019/01/01 CRDT- 2019/09/27 06:00 PHST- 2019/05/20 00:00 [received] PHST- 2019/08/12 00:00 [accepted] PHST- 2019/09/27 06:00 [entrez] PHST- 2019/09/27 06:00 [pubmed] PHST- 2019/09/27 06:01 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - 10.3389/fnsyn.2019.00025 [doi] PST - epublish SO - Front Synaptic Neurosci. 2019 Aug 29;11:25. doi: 10.3389/fnsyn.2019.00025. eCollection 2019.