Abstract
Protein scaffolds are essential for specific and efficient downstream signaling at synapses. Though nicotinic receptors are widely expressed in the nervous system and influence numerous cellular events due in part to their calcium permeability, no scaffolds have yet been identified for the receptors in neurons. Here we show that specific members of the PSD-95 family of PDZ-containing proteins are associated with specific nicotinic receptor subtypes. At postsynaptic sites, the PDZ scaffolds are essential for maturation of functional nicotinic synapses on neurons. They also help mediate downstream signaling as exemplified by activation of transcription factors. By tethering components to postsynaptic nicotinic receptors, PDZ scaffolds can organize synaptic structure and determine which calcium-dependent processes will be subject to nicotinic modulation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Calcium Signaling / genetics
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Cell Differentiation / genetics*
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Cells, Cultured
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Central Nervous System / cytology
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Central Nervous System / growth & development*
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Central Nervous System / metabolism
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Cyclic AMP Response Element-Binding Protein / genetics
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Cyclic AMP Response Element-Binding Protein / metabolism
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Cytoskeleton / metabolism*
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DNA, Complementary / analysis
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DNA, Complementary / genetics
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Disks Large Homolog 4 Protein
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / genetics
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Ganglia, Parasympathetic / cytology
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Ganglia, Parasympathetic / metabolism
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Guanylate Kinases
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Mice
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Mice, Inbred BALB C
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Nerve Tissue Proteins / metabolism*
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Neurons / cytology
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Neurons / metabolism*
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Phylogeny
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Protein Structure, Tertiary / genetics
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Receptors, Nicotinic / metabolism*
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SAP90-PSD95 Associated Proteins
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Sequence Homology, Nucleic Acid
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Signal Transduction / genetics
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Synaptic Membranes / metabolism*
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Synaptic Transmission / genetics
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Transcription Factors / genetics
Substances
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Cyclic AMP Response Element-Binding Protein
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DNA, Complementary
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Disks Large Homolog 4 Protein
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Dlg4 protein, mouse
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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Receptors, Nicotinic
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SAP90-PSD95 Associated Proteins
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Transcription Factors
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postsynaptic density proteins
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Guanylate Kinases