Activity-Dependent Palmitoylation Controls SynDIG1 Stability, Localization, and Function

Autor: Elva D Diaz, Kristopher E. Plambeck, Inderpreet Kaur, Eden V. Barragan, Eric S. Ontiveros, Lyndsey M. Kirk, Vladimir Yarov-Yarovoy
Rok vydání: 2016
Předmět:
Models
Molecular
0301 basic medicine
excitatory synapse
Inbred C57BL
Hippocampus
Medical and Health Sciences
Rats
Sprague-Dawley
Synapse
Mice
SynDIG1
Pregnancy
Models
Chlorocebus aethiops
Premovement neuronal activity
palmitoylation
Gap-43 protein
Cells
Cultured
Neurons
Cultured
General Neuroscience
Transmembrane protein
Cell biology
Protein Transport
Neurological
Female
Brief Communications
Cells
Lipoylation
1.1 Normal biological development and functioning
Nerve Tissue Proteins
Tetrodotoxin
AMPA receptor
In Vitro Techniques
Biology
Cercopithecus aethiops
03 medical and health sciences
Organ Culture Techniques
Excitatory synapse
Palmitoylation
Underpinning research
Animals
PSD-95
Neurology & Neurosurgery
Psychology and Cognitive Sciences
Neurosciences
Membrane Proteins
Molecular
Subcellular localization
Rats
Mice
Inbred C57BL
030104 developmental biology
Gene Expression Regulation
nervous system
Synapses
biology.protein
Sprague-Dawley
Zdroj: The Journal of neuroscience : the official journal of the Society for Neuroscience, vol 36, iss 29
Kaur, I; Yarov-Yarovoy, V; Kirk, LM; Plambeck, KE; Barragan, EV; Ontiveros, ES; et al.(2016). Activity-dependent palmitoylation controls synDIG1 stability, localization, and function. Journal of Neuroscience, 36(29), 7562-7568. doi: 10.1523/JNEUROSCI.4859-14.2016. UC Davis: Retrieved from: http://www.escholarship.org/uc/item/74f5p0xr
ISSN: 1529-2401
0270-6474
DOI: 10.1523/jneurosci.4859-14.2016
Popis: UnlabelledSynapses are specialized contacts between neurons. Synapse differentiation-induced gene I (SynDIG1) plays a critical role during synapse development to regulate AMPA receptor (AMPAR) and PSD-95 content at excitatory synapses. Palmitoylation regulates the localization and function of many synaptic proteins, including AMPARs and PSD-95. Here we show that SynDIG1 is palmitoylated, and investigate the effects of palmitoylation on SynDIG1 stability and localization. Structural modeling of SynDIG1 suggests that the membrane-associated region forms a three-helical bundle with two cysteine residues located at positions 191 and 192 in the juxta-transmembrane region exposed to the cytoplasm. Site-directed mutagenesis reveals that C191 and C192 are palmitoylated in heterologous cells and positively regulates dendritic targeting in neurons. Like PSD-95, activity blockade in a rat hippocampal slice culture increases SynDIG1 palmitoylation, which is consistent with our prior demonstration that SynDIG1 localization at synapses increases upon activity blockade. These data demonstrate that palmitoylation of SynDIG1 is regulated by neuronal activity, and plays a critical role in regulating its stability and subcellular localization, and thereby its function.Significance statementPalmitoylation is a reversible post-translation modification that has recently been recognized as playing a critical role in the localization and function of many synaptic proteins. Here we show that activity-dependent palmitoylation of the atypical AMPA receptor auxiliary transmembrane protein SynDIG1 regulates its stability and localization at synapses to regulate function and synaptic strength.
Databáze: OpenAIRE
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