Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Brain Chemistry / physiology
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COS Cells
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Cells, Cultured
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Chlorocebus aethiops
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Dendrites / drug effects
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Dendrites / metabolism
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Disks Large Homolog 4 Protein
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Electrophysiology
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Green Fluorescent Proteins / metabolism
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Guanylate Kinases
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Hippocampus / cytology
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Hippocampus / drug effects
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Hippocampus / metabolism
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Intracellular Signaling Peptides and Proteins / metabolism
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Membrane Proteins / metabolism
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Mice
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Mice, Knockout
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Molecular Sequence Data
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Multigene Family / genetics*
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Neurons / metabolism
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Patch-Clamp Techniques
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RNA, Messenger / biosynthesis
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RNA, Small Interfering / genetics
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Receptors, AMPA / metabolism
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Receptors, N-Methyl-D-Aspartate / metabolism
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Receptors, N-Methyl-D-Aspartate / physiology
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Reverse Transcriptase Polymerase Chain Reaction
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Synapses / physiology*
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Transfection
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Up-Regulation / physiology
Substances
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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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RNA, Messenger
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RNA, Small Interfering
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Receptors, AMPA
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Receptors, N-Methyl-D-Aspartate
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Green Fluorescent Proteins
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Guanylate Kinases
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glutamate receptor ionotropic, AMPA 1
Associated data
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GENBANK/EF651798
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GENBANK/EF651799
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GENBANK/EF651800
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GENBANK/EF651801
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GENBANK/EF651802
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GENBANK/EF651803
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GENBANK/EF651804
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GENBANK/EF651805
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GENBANK/EF651806
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GENBANK/EF651807
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GENBANK/EF651808
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GENBANK/EF651811
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GENBANK/EF651814
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GENBANK/EF651818
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GENBANK/EF651819
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GENBANK/EF651820
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GENBANK/EF651821
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GENBANK/EF651822
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GENBANK/EF651842
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GENBANK/EF651843