Abstract
Long-term potentiation (LTP) is accompanied by dendritic spine growth and changes in the composition of the postsynaptic density (PSD). We find that activity-dependent growth of apical spines of CA1 pyramidal neurons is accompanied by destabilization of the PSD that results in transient loss and rapid replacement of PSD-95 and SHANK2. Signaling through PSD-95 is required for activity-dependent spine growth and trafficking of SHANK2. N-terminal PDZ and C-terminal guanylate kinase domains of PSD-95 are required for both processes, indicating that PSD-95 coordinates multiple signals to regulate morphological plasticity. Activity-dependent trafficking of PSD-95 is triggered by phosphorylation at serine 73, a conserved calcium/calmodulin-dependent protein kinase II (CaMKII) consensus phosphorylation site, which negatively regulates spine growth and potentiation of synaptic currents. We propose that PSD-95 and CaMKII act at multiple steps during plasticity induction to initially trigger and later terminate spine growth by trafficking growth-promoting PSD proteins out of the active spine.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives
-
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
-
Animals
-
Animals, Newborn
-
Dendritic Spines / drug effects
-
Dendritic Spines / physiology*
-
Disks Large Homolog 4 Protein
-
Electric Stimulation / methods
-
Enzyme Inhibitors / pharmacology
-
Excitatory Amino Acid Antagonists / pharmacology
-
Glutamates / pharmacology
-
Green Fluorescent Proteins / biosynthesis
-
Green Fluorescent Proteins / genetics
-
Hippocampus / cytology
-
Indoles / pharmacology
-
Intracellular Signaling Peptides and Proteins / genetics
-
Intracellular Signaling Peptides and Proteins / metabolism*
-
Long-Term Potentiation / physiology
-
Membrane Proteins / genetics
-
Membrane Proteins / metabolism*
-
Nerve Tissue Proteins / metabolism
-
Neuronal Plasticity / drug effects
-
Neuronal Plasticity / physiology*
-
Neurons / cytology*
-
Neurons / drug effects
-
Organ Culture Techniques
-
Patch-Clamp Techniques / methods
-
Phosphorylation / drug effects
-
Phosphorylation / physiology
-
Piperazines / pharmacology
-
Point Mutation
-
Protein Structure, Tertiary
-
Protein Transport / drug effects
-
Rats
-
Rats, Sprague-Dawley
-
Serine / metabolism*
-
Time Factors
Substances
-
4-methoxy-7-nitroindolinyl-glutamate
-
Disks Large Homolog 4 Protein
-
Dlg4 protein, rat
-
Enzyme Inhibitors
-
Excitatory Amino Acid Antagonists
-
Glutamates
-
Indoles
-
Intracellular Signaling Peptides and Proteins
-
Membrane Proteins
-
Nerve Tissue Proteins
-
Piperazines
-
Shank2 protein, rat
-
Green Fluorescent Proteins
-
Serine
-
KN 62
-
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
-
3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid