Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylation Export

@article{19503082, abstract = {The insertion of AMPA receptors (AMPARs) into the plasma membrane is an important step in the synaptic delivery of AMPARs during the expression of synaptic plasticity. However, the molecular mechanisms regulating AMPAR insertion remain elusive. By directly visualizing individual insertion events of the AMPAR subunit GluR1 in rodents, we found that the protein 4.1N was required for activity-dependent GluR1 insertion. Protein kinase C (PKC) phosphorylation of the serine 816 (S816) and S818 residues of GluR1 enhanced 4.1N binding to GluR1 and facilitated GluR1 insertion. In addition, palmitoylation of GluR1 C811 residue modulated PKC phosphorylation and GluR1 insertion. Finally, disrupting 4.1N-dependent GluR1 insertion decreased surface expression of GluR1 and the expression of long-term potentiation. Our study uncovers a previously unknown mechanism that governs activity-dependent GluR1 trafficking, reveals an interaction between AMPAR palmitoylation and phosphorylation, and underscores the functional importance of 4.1N in AMPAR trafficking and synaptic plasticity.}, address = {Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.}, author = {Lin, D. T. and Makino, Y. and Sharma, K. and Hayashi, T. and Neve, R. and Takamiya, K. and Huganir, R. L.}, citeulike-article-id = {5378169}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nn.2351}, citeulike-linkout-1 = {http://www.nature.com/neuro/journal/v12/n7/abs/nn.2351.html}, comment = {Note}, day = {1}, doi = {10.1038/nn.2351}, issn = {1097-6256}, journal = {Nature Neuroscience}, keywords = {ampar, exocytosis, hippo-neurons-culture, phosphorylation, surface-expression, tirf}, month = {July}, number = {7}, pages = {879--87}, pdf = {file://localhost/Users/christo/Travail/Labo/Biblio/Papers/Lin\_Nat\%20Neurosci\_2009.pdf}, posted-at = {2009-08-06 10:14:26}, priority = {0}, publisher = {Nature Publishing Group}, title = {Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylation}, url = {http://dx.doi.org/10.1038/nn.2351}, volume = {12}, year = {2009} }

TY - JOUR ID - 19503082 L3 - citeulike-article-id:5378169 N2 - The insertion of AMPA receptors (AMPARs) into the plasma membrane is an important step in the synaptic delivery of AMPARs during the expression of synaptic plasticity. However, the molecular mechanisms regulating AMPAR insertion remain elusive. By directly visualizing individual insertion events of the AMPAR subunit GluR1 in rodents, we found that the protein 4.1N was required for activity-dependent GluR1 insertion. Protein kinase C (PKC) phosphorylation of the serine 816 (S816) and S818 residues of GluR1 enhanced 4.1N binding to GluR1 and facilitated GluR1 insertion. In addition, palmitoylation of GluR1 C811 residue modulated PKC phosphorylation and GluR1 insertion. Finally, disrupting 4.1N-dependent GluR1 insertion decreased surface expression of GluR1 and the expression of long-term potentiation. Our study uncovers a previously unknown mechanism that governs activity-dependent GluR1 trafficking, reveals an interaction between AMPAR palmitoylation and phosphorylation, and underscores the functional importance of 4.1N in AMPAR trafficking and synaptic plasticity. IS - 7 JF - Nature Neuroscience SN - 1097-6256 AD - Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. EP - 87 TI - Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylation PB - Nature Publishing Group VL - 12 SP - 879 KW - ampar KW - exocytosis KW - hippo-neurons-culture KW - phosphorylation KW - surface-expression KW - tirf N1 - Note AU - Lin, DT AU - Makino, Y AU - Sharma, K AU - Hayashi, T AU - Neve, R AU - Takamiya, K AU - Huganir, RL PY - 2009/07/01/ UR - http://dx.doi.org/10.1038/nn.2351 ER -