451.2 - Palmitoylation-dependent Regulation of Axonal Protein Trafficking in Neurons
Tuesday, April 5, 2022
3:35 PM – 4:00 PM
Room: 204 B - Pennsylvania Convention Center
Introduction: Protein S-palmitoylation is a post-translational modification, whereby a fatty acyl chain, usually palmitoyl, is attached to cysteine thiol groups in proteins. The increase in local hydrophobicity promotes binding of cytosolic proteins to organelle and plasma membranes. S-palmitoylation of integral membrane proteins can promote their segregation into liquid-ordered (raft) domains. Therefore, S-palmitoylation impacts on proteins distribution and function. Due to the advancement in experimental techniques for detecting and quantifying protein S-palmitoylation, our understanding of the scope and functional roles of protein S-palmitoylation has progressed profoundly in recent years. High-throughput experiments have defined palmitoyl-proteomes, or palmitoylomes, of various cell types and from different species. The current version of SwissPalm, a public repository of information on protein palmitoylation, reports 4,587 human proteins collectively identified in 17 human palmitoylomes, accounting for 19.5% of human proteins in its database. The prevalence of protein S-palmitoylation indicates that this PTM is involved in many aspects of cellular function. Protein S-palmitoylation is mediated by the so-called DHHC (or zDHHC) enzymes, because of their shared aspartate-histidine-histidine-cysteine, or DHHC, motif. Human has 23 DHHC genes. Mutations in DHHC genes have been linked to neurological disorders and cancers, pointing to their importance in human physiology and diseases. Efforts have been under way to design small molecule DHHC modulators as therapeutic agents for human disorders.
