Characterization of Takusan, a Novel Gene Family that Regulates Synaptic Activity
Autor: | Tu, Shichun, Shin, Yeonsook, Zago, Wagner M., States, Bradley A., Eroshkin, Alexey, Lipton, Stuart A., Tong, Gary G., Nakanishi, Nobuki |
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Jazyk: | angličtina |
Rok vydání: | 2007 |
Předmět: |
Patch-Clamp Techniques
Green Fluorescent Proteins Molecular Sequence Data Transfection Hippocampus Receptors N-Methyl-D-Aspartate Article Mice Chlorocebus aethiops Animals Amino Acid Sequence RNA Messenger Receptors AMPA RNA Small Interfering Cells Cultured Brain Chemistry Mice Knockout Neurons Reverse Transcriptase Polymerase Chain Reaction Intracellular Signaling Peptides and Proteins Membrane Proteins Dendrites Up-Regulation Electrophysiology nervous system Multigene Family COS Cells Synapses Disks Large Homolog 4 Protein Guanylate Kinases |
Popis: | We have characterized a rodent-specific gene family designated alpha-takusan (meaning "many" in Japanese). We initially identified a member of the family whose expression is upregulated in mice lacking the NMDAR subunit NR3A. We then isolated cDNAs encoding 46 alpha-takusan variants from mouse brains. Most variants share an approximately 130 aa long sequence, which contains the previously identified domain of unknown function 622 (DUF622) and is predicted to form coiled-coil structures. Single-cell PCR analyses indicate that one neuron can express multiple alpha-takusan variants and particular variants may predominate in certain cell types. Forced expression in cultured hippocampal neurons of two variants, alpha1 or alpha2, which bind either directly or indirectly to PSD-95, leads to an increase in PSD-95 clustering, dendritic spine density, GluR1 surface expression, and AMPAR activity. Conversely, treating cultured neurons with RNAi targeting alpha-takusan variants resulted in the opposite phenotype. Hence, alpha-takusan represents a large gene family that regulates synaptic activity. |
Databáze: | OpenAIRE |
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