scholarly journals Neuronal activity moves protein palmitoylation into the synapse

2009 ◽  
Vol 186 (1) ◽  
pp. 7-9 ◽  
Author(s):  
Matthew B. Dalva
Keyword(s):  
Subcellular Localization ◽  
Large Class ◽  
Neuronal Activity ◽  
Lipid Modification ◽  
Cell Biol ◽  
Protein Palmitoylation ◽  
Neuronal Proteins ◽  
Specific Proteins

Many neuronal proteins undergo lipid modification that regulates their function and subcellular localization. One such modification is palmitoylation, which is mediated by a large class of protein palmitoyl acyltransferases (PATs). Now, a paper in this issue (Noritake et al. 2009. J. Cell Biol. doi:10.1083/jcb.200903101) demonstrates that the localization of the PAT DHHC2 is regulated by neuronal activity and thereby selectively controls the palmitoylation and subsequent accumulation of specific proteins in the synapse.

scholarly journals Palmitoylation as a Functional Regulator of Neurotransmitter Receptors

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Vladimir S. Naumenko ◽  
Evgeni Ponimaskin
Keyword(s):  
Posttranslational Modifications ◽  
Current Knowledge ◽  
Point Of View ◽  
Covalent Attachment ◽  
Neurotransmitter Receptors ◽  
Protein Palmitoylation ◽  
Neuronal Proteins ◽  
Functional Point ◽  
Pathological Behavior ◽  
Multiple Signaling

The majority of neuronal proteins involved in cellular signaling undergo different posttranslational modifications significantly affecting their functions. One of these modifications is a covalent attachment of a 16-C palmitic acid to one or more cysteine residues (S-palmitoylation) within the target protein. Palmitoylation is a reversible modification, and repeated cycles of palmitoylation/depalmitoylation might be critically involved in the regulation of multiple signaling processes. Palmitoylation also represents a common posttranslational modification of the neurotransmitter receptors, including G protein-coupled receptors (GPCRs) and ligand-gated ion channels (LICs). From the functional point of view, palmitoylation affects a wide span of neurotransmitter receptors activities including their trafficking, sorting, stability, residence lifetime at the cell surface, endocytosis, recycling, and synaptic clustering. This review summarizes the current knowledge on the palmitoylation of neurotransmitter receptors and its role in the regulation of receptors functions as well as in the control of different kinds of physiological and pathological behavior.

scholarly journals Mcp4, a Meiotic Coiled-Coil Protein, Plays a Role in F-Actin Positioning during Schizosaccharomyces pombe Meiosis

2007 ◽  
Vol 6 (6) ◽  
pp. 971-983 ◽  
Author(s):  
Ayami Ohtaka ◽  
Daisuke Okuzaki ◽  
Takamune T. Saito ◽  
Hiroshi Nojima
Keyword(s):  
Subcellular Localization ◽  
Schizosaccharomyces Pombe ◽  
Coiled Coil ◽  
Microscopic Analysis ◽  
Specific Protein ◽  
Membrane Formation ◽  
Meiotic Progression ◽  
Specific Proteins ◽  
Fluorescence Microscopic Analysis

ABSTRACT Some meiosis-specific proteins of Schizosaccharomyces pombe harbor coiled-coil motifs and play essential roles in meiotic progression. Here we describe Mcp4, a novel meiosis-specific protein whose expression is abruptly induced at the horsetail phase and which remains expressed until sporulation is finished. Fluorescence microscopic analysis revealed that Mcp4 alters its subcellular localization during meiosis in a manner that partially resembles the movement of F-actin during meiosis. Mcp4 and F-actin never colocalize; rather, they are located in a side-by-side manner. When forespore membrane formation begins at metaphase II, the Mcp4 signals assemble at the lagging face of the dividing nuclei. At this stage, they are sandwiched between F-actin and the nucleus. Mcp4, in turn, appears to sandwich F-actin with Meu14. In mcp4Δ cells at anaphase II, the F-actin, which is normally dumbbell-shaped, adopts an abnormal balloon shape. Spores of mcp4Δ cells were sensitive to NaCl, although their shape and viability were normal. Taken together, we conclude that Mcp4 plays a role in the accurate positioning of F-actin during S. pombe meiosis.

scholarly journals Regulation of Dendritic Branching and Filopodia Formation in Hippocampal Neurons by Specific Acylated Protein Motifs

2004 ◽  
Vol 15 (5) ◽  
pp. 2205-2217 ◽  
Author(s):  
Catherine Gauthier-Campbell ◽  
David S. Bredt ◽  
Timothy H. Murphy ◽  
Alaa El-Din El-Husseini
Keyword(s):  
Hippocampal Neurons ◽  
Active Form ◽  
Dominant Negative ◽  
Protein Motifs ◽  
C Terminus ◽  
Dominant Negative Form ◽  
Protein Palmitoylation ◽  
Dendritic Branching ◽  
Neuronal Proteins ◽  
Neuronal Processes

Although neuronal axons and dendrites with their associated filopodia and spines exhibit a profound cell polarity, the mechanism by which they develop is largely unknown. Here, we demonstrate that specific palmitoylated protein motifs, characterized by two adjacent cysteines and nearby basic residues, are sufficient to induce filopodial extensions in heterologous cells and to increase the number of filopodia and the branching of dendrites and axons in neurons. Such motifs are present at the N-terminus of GAP-43 and the C-terminus of paralemmin, two neuronal proteins implicated in cytoskeletal organization and filopodial outgrowth. Filopodia induction is blocked by mutations of the palmitoylated sites or by treatment with 2-bromopalmitate, an agent that inhibits protein palmitoylation. Moreover, overexpression of a constitutively active form of ARF6, a GTPase that regulates membrane cycling and dendritic branching reversed the effects of the acylated protein motifs. Filopodia induction by the specific palmitoylated motifs was also reduced upon overexpression of a dominant negative form of the GTPase cdc42. These results demonstrate that select dually lipidated protein motifs trigger changes in the development and growth of neuronal processes.

scholarly journals Mobile DHHC palmitoylating enzyme mediates activity-sensitive synaptic targeting of PSD-95

2009 ◽  
Vol 186 (1) ◽  
pp. 147-160 ◽  
Author(s):  
Jun Noritake ◽  
Yuko Fukata ◽  
Tsuyoshi Iwanaga ◽  
Naoki Hosomi ◽  
Ryouhei Tsutsumi ◽  
...  
Keyword(s):  
Protein Trafficking ◽  
Large Family ◽  
Synaptic Activity ◽  
Lipid Modification ◽  
Synaptic Targeting ◽  
Extracellular Signals ◽  
Acid Type ◽  
Protein Palmitoylation ◽  
Intracellular Compartments ◽  
Synaptic Clustering

Protein palmitoylation is the most common posttranslational lipid modification; its reversibility mediates protein shuttling between intracellular compartments. A large family of DHHC (Asp-His-His-Cys) proteins has emerged as protein palmitoyl acyltransferases (PATs). However, mechanisms that regulate these PATs in a physiological context remain unknown. In this study, we efficiently monitored the dynamic palmitate cycling on synaptic scaffold PSD-95. We found that blocking synaptic activity rapidly induces PSD-95 palmitoylation and mediates synaptic clustering of PSD-95 and associated AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-type glutamate receptors. A dendritically localized DHHC2 but not the Golgi-resident DHHC3 mediates this activity-sensitive palmitoylation. Upon activity blockade, DHHC2 translocates to the postsynaptic density to transduce this effect. These data demonstrate that individual DHHC members are differentially regulated and that dynamic recruitment of protein palmitoylation machinery enables compartmentalized regulation of protein trafficking in response to extracellular signals.

scholarly journals Neurexin nanoclusters: A novel structure at presynaptic terminals

2019 ◽  
Vol 218 (8) ◽  
pp. 2442-2443
Author(s):  
Daichi Kawaguchi ◽  
Yukiko Gotoh
Keyword(s):  
Cell Adhesion ◽  
High Resolution ◽  
Subcellular Localization ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Presynaptic Terminals ◽  
Cell Biol ◽  
Novel Structure ◽  
Synaptic Functions ◽  
Nanoscale Clusters

The trans-synaptic cell adhesion molecule neurexin regulates synaptic functions but its high-resolution subcellular localization and dynamics were unknown. Trotter et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201812076) describe previously unrecognized nanoscale clusters of neurexin-1 in presynaptic terminals and their regulation by ADAM10-mediated proteolysis.

Postsynaptic nanodomains generated by local palmitoylation cycles

2015 ◽  
Vol 43 (2) ◽  
pp. 199-204 ◽  
Author(s):  
Masaki Fukata ◽  
Atsushi Sekiya ◽  
Tatsuro Murakami ◽  
Norihiko Yokoi ◽  
Yuko Fukata
Keyword(s):  
Plasma Membrane ◽  
Protein Targeting ◽  
Scaffolding Protein ◽  
Dependent Manner ◽  
Membrane Domains ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Protein Palmitoylation ◽  
Specific Proteins

Precise regulation of protein assembly at specialized membrane domains is essential for diverse cellular functions including synaptic transmission. However, it is incompletely understood how protein clustering at the plasma membrane is initiated, maintained and controlled. Protein palmitoylation, a common post-translational modification, regulates protein targeting to the plasma membrane. Such modified proteins are enriched in these specialized membrane domains. In this review, we focus on palmitoylation of PSD-95, which is a major postsynaptic scaffolding protein and makes discrete postsynaptic nanodomains in a palmitoylation-dependent manner and discuss a determinant role of local palmitoylation cycles in creating highly localized hotspots at the membrane where specific proteins concentrate to organize functional domains.

scholarly journals Lysosomes relax in the cellular suburbs

2016 ◽  
Vol 212 (6) ◽  
pp. 617-619 ◽  
Author(s):  
Swetha Gowrishankar ◽  
Shawn M. Ferguson
Keyword(s):  
Subcellular Localization ◽  
Cellular Homeostasis ◽  
Lysosomal Ph ◽  
Cell Biol ◽  
Functional Implications ◽  
Degradative Ability

Lysosomes support cellular homeostasis by degrading macromolecules and recycling nutrients. In this issue, Johnson et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201507112) reveal a heterogeneity in lysosomal pH and degradative ability that correlates with lysosome subcellular localization, raising questions about the functional implications and mechanisms underlying these observations.

scholarly journals Subcellular Golgi localization of stathmin family proteins is promoted by a specific set of DHHC palmitoyl transferases

2011 ◽  
Vol 22 (11) ◽  
pp. 1930-1942 ◽  
Author(s):  
Aurore D. Levy ◽  
Véronique Devignot ◽  
Yuko Fukata ◽  
Masaki Fukata ◽  
André Sobel ◽  
...  
Keyword(s):  
Brefeldin A ◽  
Membrane Association ◽  
Lipid Modification ◽  
Subcellular Membrane ◽  
Local Functions ◽  
Peripheral Proteins ◽  
Protein Palmitoylation ◽  
Extracellular Stimuli ◽  
Cellular Compartments ◽  
Membrane Anchoring

 Protein palmitoylation is a reversible lipid modification that plays critical roles in protein sorting and targeting to specific cellular compartments. The neuronal microtubule-regulatory phosphoproteins of the stathmin family (SCG10/stathmin 2, SCLIP/stathmin 3, and RB3/stathmin 4) are peripheral proteins that fulfill specific and complementary roles in the formation and maturation of the nervous system. All neuronal stathmins are localized at the Golgi complex and at vesicles along axons and dendrites. Their membrane anchoring results from palmitoylation of two close cysteine residues present within their homologous N-terminal targeting domains. By preventing palmitoylation with 2-bromopalmitate or disrupting the integrity of the Golgi with brefeldin A, we were able to show that palmitoylation of stathmins 2 and 3 likely occurs at the Golgi and is crucial for their specific subcellular localization and trafficking. In addition, this membrane binding is promoted by a specific set of palmitoyl transferases that localize with stathmins 2 and 3 at the Golgi, directly interact with them, and enhance their membrane association. The subcellular membrane–associated microtubule-regulatory activity of stathmins might then be fine-tuned by extracellular stimuli controlling their reversible palmitoylation, which can be viewed as a crucial regulatory process for specific and local functions of stathmins in neurons.

SUMO/sentrin: protein modifiers regulating important cellular functions

1999 ◽  
Vol 77 (4) ◽  
pp. 299-309 ◽  
Author(s):  
Carole Kretz-Remy ◽  
Robert M Tanguay
Keyword(s):  
Subcellular Localization ◽  
Protein Modification ◽  
Protein Transport ◽  
Protein Localization ◽  
Cellular Functions ◽  
Nf Kappa B ◽  
Sumo Conjugation ◽  
Protein Functions ◽  
Specific Proteins ◽  
Substrate Proteins

Regulation of protein functions can be achieved by posttranslational protein modifications. One of the most studied modifications has been conjugation to ubiquitin, which mainly targets substrate proteins for degradation by the 26 S proteasome. Recently, SUMO/sentrin, a ubiquitin-like protein has been characterized. This evolutionary conserved protein is conjugated to specific proteins in a way similar, but not identical, to ubiquitin and seems also to be involved in the regulation of protein localization or function. An increasing number of SUMO/sentrin substrates are currently described. We focus here on three major substrates of modification by SUMO: RanGAP1, PML, and I(kappa)B(alpha) proteins. These different examples illustrate how SUMO conjugation may be involved in the control of the level of critical proteins within the cell or in the modulation of subcellular localization and nucleocytoplasmic trafficking.Key words: protein modification, NF-(kappa)B, I(kappa)B, protein transport, nucleus, RanGAP1, PML.

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