関: lipoylation、palmitoylate

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/10/20 01:10:09」(JST)

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In palmitoylation, a palmitoyl group (derived from palmitic acid, pictured above) is added.

Palmitoylation of a cysteine residue

Left Palmitoylation (red) anchors Ankyrin G to the plasma membrane. Right Close up. Palmityl residue in yellow.

Palmitoylation of Gephyrin Controls Receptor Clustering and Plasticity of GABAergic Synapses^[1]

Palmitoylation is the covalent attachment of fatty acids, such as palmitic acid, to cysteine and less frequently to serine and threonine residues of proteins, which are typically membrane proteins.^[2] The precise function of palmitoylation depends on the particular protein being considered. Palmitoylation enhances the hydrophobicity of proteins and contributes to their membrane association. Palmitoylation also appears to play a significant role in subcellular trafficking of proteins between membrane compartments,^[3] as well as in modulating protein–protein interactions.^[4] In contrast to prenylation and myristoylation, palmitoylation is usually reversible (because the bond between palmitic acid and protein is often a thioester bond). The reverse reaction is catalysed by palmitoyl protein thioesterases. Because palmitoylation is a dynamic, post-translational process, it is believed to be employed by the cell to alter the subcellular localization, protein–protein interactions, or binding capacities of a protein.

An example of a protein that undergoes palmitoylation is hemagglutinin, a membrane glycoprotein used by influenza to attach to host cell receptors.^[5] The palmitoylation cycles of a wide array of enzymes have been characterized in the past few years, including H-Ras, Gsα, the β2-adrenergic receptor, and endothelial nitric oxide synthase (eNOS). Another example is the major signaling protein Wnt, which is modified by a palmitoleoyl group at a serine. This is a type of O-acylation and is mediated by a membrane-bound O-acyltransferase.^[6] In signal transduction via G protein, palmitoylation of the α subunit, prenylation of the γ subunit, and myristoylation is involved in tethering the G protein to the inner surface of the plasma membrane so that the G protein can interact with its receptor.^[7]

The palmitoylome

A meta-analysis of 15 studies produced a compendium of approximately 2,000 mammalian proteins that are palmitoylated. The highest associations of the palmitoylome are with cancers and disorders of the nervous system. Approximately 40% of synaptic proteins were found in the palmitoylome.^[8]

In synaptic plasticity

Scientists have appreciated the significance of attaching long hydrophobic chains to specific proteins in cell signaling pathways. A good example of its significance is in the clustering of proteins in the synapse. A major mediator of protein clustering in the synapse is the postsynaptic density (95kD) protein PSD-95. When this protein is palmitoylated it is restricted to the membrane. This restriction to the membrane allows it to bind to and cluster ion channels in the postsynaptic membrane. Also, in the presynaptic neuron, palmitoylation of SNAP-25 directs it to partition in the cell membrane ^[9] and allows the SNARE complex to dissociate during vesicle fusion. This provides a role for palmitoylation in regulating neurotransmitter release.^[10]

Palmitoylation of delta catenin seems to coordinate activity-dependent changes in synaptic adhesion molecules, synapse structure, and receptor localizations that are involved in memory formation.^[11]

Palmitoylation of gephyrin has been reported to influence GABAergic synapses.^[1]

References

^ ^a ^b Borislav Dejanovic, Marcus Semtner, Silvia Ebert, Tobias Lamkemeyer, Franziska Neuser, Bernhard Lüscher, Jochen C. Meier, Guenter Schwarz, PLoS Biol. 2014 Jul; 12(7): e1001908. doi: 10.1371/journal.pbio.1001908. "Palmitoylation of Gephyrin Controls Receptor Clustering and Plasticity of GABAergic Synapses". journals.plos.org/. PLOS. Retrieved 4 May 2017.
^ Linder, M.E., "Reversible modification of proteins with thioester-linked fatty acids," Protein Lipidation, F. Tamanoi and D.S. Sigman, eds., pp. 215-40 (San Diego, CA: Academic Press, 2000).
^ Rocks O, Peyker A, Kahms M, Verveer PJ, Koerner C, Lumbierres M, Kuhlmann J, Waldmann H, Wittinghofer A, Bastiaens PI (2005). "An acylation cycle regulates localization and activity of palmitoylated Ras isoforms". Science. 307 (5716): 1746–1752. PMID 15705808. doi:10.1126/science.1105654.
^ Basu, J., "Protein palmitoylation and dynamic modulation of protein function," Current Science, Vol. 87, No. 2, pp. 212-17 (25 July 2004), http://www.ias.ac.in/currsci/jul252004/contents.htm
^ "INFLUENZA VIRUSES (ORTHOMYXOVIRIDAE)". Encyclopedia of Virology: 830–836. doi:10.1006/rwvi.1999.0157.
^ Takada R, Satomi Y, Kurata T, Ueno N, Norioka S, Kondoh H, Takao T, Takada S (2006). "Monounsaturated fatty acid modification of Wnt protein: its role in Wnt secretion". Dev Cell. 11 (6): 791–801. PMID 17141155. doi:10.1016/j.devcel.2006.10.003.
^ Wall, MA; Coleman, DE; Lee, E; Iñiguez-Lluhi, JA; Posner, BA; Gilman, AG; Sprang, SR (Dec 15, 1995). "The structure of the G protein heterotrimer Gi alpha 1 beta 1 gamma 2.". Cell. 83 (6): 1047–58. PMID 8521505. doi:10.1016/0092-8674(95)90220-1.
^ Sanders SS, Martin DD, Butland SL, Lavallée-Adam M, Calzolari D, Kay C, Yates JR 3rd, Hayden MR, PLoS Comput Biol. 2015 Aug 14;11(8):e1004405. doi: 10.1371/journal.pcbi.1004405. "Curation of the Mammalian Palmitoylome Indicates a Pivotal Role for Palmitoylation in Diseases and Disorders of the Nervous System and Cancers.". journals.plos.org/. PLOS. Retrieved 4 May 2017.
^ Greaves, Jennifer (March 2011). "Differential palmitoylation regulates intracellular patterning of SNAP25". Journal of Cell Science. 124 (8): 1351–1360. PMC 3065388 . PMID 21429935. doi:10.1242/jcs.079095.
^ "Molecular Mechanisms of Synaptogenesis." Edited by Alexander Dityatev and Alaa El-Husseini. Springer: New York, NY. 2006. pg. 72-75
^ Brigidi GS, Sun Y, Beccano-Kelly D, Pitman K, Jobasser M, Borgland SL, Milnerwood AJ, Bamji SX (January 23, 2014). "Palmitoylation of [delta]-catenin by DHHC5 mediates activity-induced synapse plasticity". Nature Neuroscience. 17: 522–532. doi:10.1038/nn.3657.

Smotrys J, Linder A (2004). "Palmitoylation of Intracellular Signaling Proteins: Regulation and Function". Annu Rev Biochem. 73: 559–87. PMID 15189153. doi:10.1146/annurev.biochem.73.011303.073954.
Resh, M. (2006) "Palmitoylation of Ligands, Receptors, and Intracellular Signaling Molecules". Sci STK. 359 October 31.
Linder M, Deschenes R (2007). "Palmitoylation: policing protein stability and traffic". Nature Reviews Molecular Cell Biology. 8: 74–84. PMID 17183362. doi:10.1038/nrm2084.

External links

CSS-Palm - Palmitoylation Site Prediction with a Clustering and Scoring Strategy
CKSAAP-Palm
Swisspalm - S-Palmitoylation database

UpToDate Contents

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1. T細胞受容体シグナル伝達 t cell receptor signaling

English Journal

Palmitoylation of cysteine 415 of helix 8: effect on membrane localisation and signalling of the CB(1) cannabinoid receptor.

Oddi S, Dainese E, Sandiford S, Fezza F, Lanuti M, Chiurchiu V, Totaro A, Catanzaro G, Barcaroli D, De Laurenzi V, Centonze D, Mukhopadhyay S, Selent J, Howlett AC, Maccarrone M.SourceDepartment of Biomedical Sciences, University of Teramo, Teramo, Italy. European Center for Brain Research (CERC)/Santa Lucia Foundation I.R.C.C.S., Rome, Italy. Neuroscience/Drug Abuse Research Program, Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC, USA. Department of Experimental Medicine and Biochemical Sciences, University of Rome "Tor Vergata", Rome, Italy. Department of Biomedical Sciences, University of Chieti-Pescara "G. d'Annunzio", Chieti, Italy. Department of Neurosciences, University of Rome "Tor Vergata", Rome, Italy. Research Group of biomedical Informatics (GRIB-IMIM), University of Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), Barcelona, Spain. Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
British journal of pharmacology.Br J Pharmacol.2011 Sep 6. doi: 10.1111/j.1476-5381.2011.01658.x. [Epub ahead of print]
Background and purpose:? The CB(1) cannabinoid receptor is regulated by its association with membrane microdomains like the lipid rafts. Here we investigated the role of CB(1) palmitoylation by analyzing the functional consequences of site-specific mutation of cysteine 415, the likely palmitoylate
PMID 21895628

Somatostatin receptor 5 is palmitoylated by the interacting ZDHHC5 palmitoyltransferase.

Kokkola T, Kruse C, Roy-Pogodzik EM, Pekkinen J, Bauch C, Honck HH, Hennemann H, Kreienkamp HJ.SourceInstitut fur Humangenetik, Universitatsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
FEBS letters.FEBS Lett.2011 Sep 2;585(17):2665-70. Epub 2011 Jul 31.
Many G-protein coupled receptors are palmitoylated in their C-terminal, intracellular regions. So far no enzymes responsible for this modification have been described. We identified an interaction of the membrane proximal helix 8 of somatostatin receptor 5 (SSTR5) with the N-terminal region of the p
PMID 21820437

Japanese Journal

Modification and Translocation of Rac/Rop Guanosine 5′-Triphosphate-Binding Proteins of Scoparia dulcis in Response to Stimulation with Methyl Jasmonate

Mitamura Toshiaki,Yamamura Yoshimi,Kurosaki Fumiya
Biological & Pharmaceutical Bulletin 34(6), 845-849, 2011
… These results suggest that both Sdrac-1 and Sdrac-2 translocate to plant membranes by the stimulation with methyl jasmonate, however, targeting of these proteins is triggered by the independent modification mechanisms, palmitoylation for Sdrac-1 and prenylation for Sdrac-2. …
NAID 130000738059

Palmitoylation of the sphingosine 1-phosphate receptor S1P1 is involved in its signaling functions and internalization

Ohno Yusuke,Ito Ayako,Ogata Ren,Hiraga Yuki,Igarashi Yasuyuki,Kihara Akio
Genes to Cells 14(8), 911-923, 2009-08
… We examined the roles of palmitoylation of S1P1 using model cells in which wild type S1P1 or a non-palmitoylated mutant S1P1 was overproduced. … Finally, palmitoylation of wild type S1P1 increased upon treatment with S1P, suggesting that S1P1 undergoes a palmitoylation/depalmitoylation cycle after stimulation by its ligands. …
NAID 120001840100