The X-linked intellectual disability protein TSPAN7 regulates excitatory synapse development and AMPAR trafficking.
Mutations in TSPAN7--a member of the tetraspanin protein superfamily--are implicated in some forms of X-linked intellectual disability. Here we show that TSPAN7 overexpression promotes the formation of filopodia and dendritic spines in cultured hippocampal neurons from embryonic rats, whereas TSPAN7 silencing reduces head size and stability of spines and AMPA ... receptor currents. Via its C terminus, TSPAN7 interacts with the PDZ domain of protein interacting with C kinase 1 (PICK1), to regulate PICK1 and GluR2/3 association and AMPA receptor trafficking. These findings indicate that, in hippocampal neurons, TSPAN7 regulates AMPA receptor trafficking by limiting PICK1 accessibility to AMPA receptors and suggest an additional mechanism for the functional maturation of glutamatergic synapses, whose impairment is implicated in intellectual disability.
Mesh Terms:
Analysis of Variance, Animals, Biophysics, Carrier Proteins, Cells, Cultured, Chlorocebus aethiops, Dendritic Spines, Disks Large Homolog 4 Protein, Electric Stimulation, Embryo, Mammalian, Excitatory Postsynaptic Potentials, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Hippocampus, Humans, Hydrazones, Immunoprecipitation, In Vitro Techniques, Integrin beta1, Intracellular Signaling Peptides and Proteins, Long-Term Potentiation, Membrane Proteins, Microscopy, Confocal, Nerve Tissue Proteins, Neurons, Nuclear Proteins, Patch-Clamp Techniques, Protein Transport, Pseudopodia, RNA, Small Interfering, Rats, Receptors, AMPA, Synapses, Tetraspanins, Time Factors, Transfection, Two-Hybrid System Techniques
Analysis of Variance, Animals, Biophysics, Carrier Proteins, Cells, Cultured, Chlorocebus aethiops, Dendritic Spines, Disks Large Homolog 4 Protein, Electric Stimulation, Embryo, Mammalian, Excitatory Postsynaptic Potentials, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Hippocampus, Humans, Hydrazones, Immunoprecipitation, In Vitro Techniques, Integrin beta1, Intracellular Signaling Peptides and Proteins, Long-Term Potentiation, Membrane Proteins, Microscopy, Confocal, Nerve Tissue Proteins, Neurons, Nuclear Proteins, Patch-Clamp Techniques, Protein Transport, Pseudopodia, RNA, Small Interfering, Rats, Receptors, AMPA, Synapses, Tetraspanins, Time Factors, Transfection, Two-Hybrid System Techniques
Neuron
Date: Mar. 22, 2012
PubMed ID: 22445342
View in: Pubmed Google Scholar
Download Curated Data For This Publication
249190
Switch View:
- Interactions 8