Postsynaptic protein mobility in dendritic spines: long-term regulation by synaptic NMDA receptor activation.
Reorganization of molecular components represents a cellular mechanism for synaptic plasticity. Dendritic spines, major sites for glutamatergic synapses, compartmentalize dynamic changes in molecular composition. Here, we use fluorescence recovery after photobleaching (FRAP) in cultured hippocampal neurons to show that spine proteins undergo continual exchange with extra-spine pools. Each spine component has a distinctive mobility: calcium/calmodulin activated protein kinase CaMKIIalpha > GluR1 AMPA glutamate receptor > PSD-95 scaffolding protein > NR1 NMDA glutamate receptor. Stimulation of synaptic NMDA receptors by a protocol that induces chemical LTP resulted in a long-lasting reduction in the mobility of spine CaMKIIalpha and an increased mobile fraction but slower kinetics for spine GluR1. Stimulation also increased the resistance of postsynaptic CaMKIIalpha to detergent extraction. These results suggest long-lasting changes in affinity of protein-protein interactions and/or ongoing alterations in exo/endocytosis. Such lasting changes in protein mobility may contribute to maintaining alterations in synaptic efficacy.
Sharma
Kamal
K
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA. ksharma5@jhem.jhmi.edu
Fong
Dan K
DK
Craig
Ann Marie
AM
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000737:chemistry / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D006624:Hippocampus / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013569:Synapses / Q000737:chemistry / Q000502:physiology*
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; C501449:Dlg4 protein, rat; C409466:NR1 NMDA receptor; C033652:postsynaptic density proteins