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Front. Synaptic Neurosci. | doi: 10.3389/fnsyn.2019.00025

Depalmitoylation by palmitoyl-protein thioesterase 1 in neuronal health and degeneration

  • 1Department of Anatomy&Cell Biology, University of Illinois at Chicago, United States
  • 2Department of Anatomy & Cell Biology, University of Illinois at Chicago, United States

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, / hydrolase domain-containing 17 proteins, 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.

Keywords: palmitoylation, Depalmitoylation, PPT1, Neuronal ceroid lipofuscinoses (NCL), NMDA - receptor, neurodegeneration

Received: 20 May 2019; Accepted: 12 Aug 2019.

Copyright: © 2019 Koster and Yoshii. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Akira Yoshii, University of Illinois at Chicago, Department of Anatomy & Cell Biology, Chicago, 60612, IL, United States, ayoshii@uic.edu