title: Local Palmitoylation Cycles and Specialized Membrane Domain Organization.
abstract: Palmitoylation is an evolutionally conserved lipid modification of proteins. Dynamic and reversible palmitoylation controls a wide range of molecular and cellular properties of proteins including the protein trafficking, protein function, protein stability, and specialized membrane domain organization. However, technical difficulties in (1) detection of palmitoylated substrate proteins and (2) purification and enzymology of palmitoylating enzymes have prevented the progress in palmitoylation research, compared with that in phosphorylation research. The recent development of proteomic and chemical biology techniques has unexpectedly expanded the known complement of palmitoylated proteins in various species and tissues/cells, and revealed the unique occurrence of palmitoylated proteins in membrane-bound organelles and specific membrane compartments. Furthermore, identification and characterization of DHHC (Asp-His-His-Cys) palmitoylating enzyme-substrate pairs have contributed to elucidating the regulatory mechanisms and pathophysiological significance of protein palmitoylation. Here, we review the recent progress in protein palmitoylation at the molecular, cellular, and in vivo level and discuss how locally regulated palmitoylation machinery works for dynamic nanoscale organization of membrane domains.
authors.affiliation: Division of Membrane Physiology, Department of Cell Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Department of Physiological Sciences, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fukata
authors.affiliation: Division of Membrane Physiology, Department of Cell Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Department of Physiological Sciences, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Murakami
authors.affiliation: Division of Membrane Physiology, Department of Cell Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Department of Physiological Sciences, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Yokoi
authors.affiliation: Division of Membrane Physiology, Department of Cell Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Department of Physiological Sciences, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Fukata
mesh_terms: D000818:Animals; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D054878:Lipoylation; D021962:Membrane Microdomains / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism
chemical_list: D011506:Proteins
keywords: Acylation; DHHC/ZDHHC protein; Depalmitoylation; Membrane domain; Microdomain; Nanodomain; PSD; PSD-95; Palmitoylation; Synapse