Takusan: A Large Gene Family that Regulates Synaptic Activity

• Published in: Neuron (Cambridge, Mass.) Vol. 55; no. 1; pp. 69 - 85
• Main Authors: Tu, Shichun, Shin, Yeonsook, Zago, Wagner M., States, Bradley A., Eroshkin, Alexey, Lipton, Stuart A., Tong, Gary G., Nakanishi, Nobuki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.07.2007; Elsevier Limited
• Subjects: Amino Acid Sequence; Animals; Brain Chemistry - physiology; Brain research; Cell culture; CELLBIO; Cells, Cultured; Cercopithecus aethiops; COS Cells; Dendrites - drug effects; Dendrites - metabolism; Disks Large Homolog 4 Protein; Electrophysiology; Experiments; Genes; Genomes; Green Fluorescent Proteins - metabolism; Guanylate Kinases; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - metabolism; Intracellular Signaling Peptides and Proteins - metabolism; Kinases; Membrane Proteins - metabolism; Mice; Mice, Knockout; Molecular Sequence Data; MOLNEURO; Multigene Family - genetics; Neurons; Neurons - metabolism; Patch-Clamp Techniques; PROTEINS; Receptors, AMPA - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; Receptors, N-Methyl-D-Aspartate - physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Small Interfering - genetics; Rodents; Synapses - physiology; Transfection; Up-Regulation - physiology; CELLBIO; PROTEINS; MOLNEURO
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2007.06.021

We have characterized a rodent-specific gene family designated α-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 α-takusan variants from mouse brains. Most variants share an ∼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 α-takusan variants and particular variants may predominate in certain cell types. Forced expression in cultured hippocampal neurons of two variants, α1 or α2, 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 α-takusan variants resulted in the opposite phenotype. Hence, α-takusan represents a large gene family that regulates synaptic activity.