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第67回 東京大学遺伝子実験施設セミナー

介頂きます。[参考文献:Neuron 55(1)&s_comma; 69-85 (2007)]

日時:平成19年7月31日(火) 14:00-15:00

Takusan&s_comma; a Novel Gene Family that Regulates Synaptic Activity

Nobuki Nakanishi (Center for Neuroscience and Aging&s_comma; Burnham Institute of
Medical Research&s_comma; La Jolla&s_comma; California&s_comma; USA)

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 a ~130-aa long sequence&s_comma;
which contains the previously identified DUF622 (domain of unknown function
622) and is predicted to form coiled-coil structures. Single-cell PCR
analyses indicate one neuron can express multiple alpha-takusan variants&s_comma;
and particular variants may predominate in certain cell types. Forced
expression in cultured hippocampal neurons of two variants&s_comma; alpha1 or
alpha2&s_comma; which bind either directly or indirectly to PSD-95&s_comma; leads to an
increase in PSD-95 clustering&s_comma; dendritic-spine density&s_comma; GluR1 surface
expression&s_comma; and AMPAR activity. Conversely&s_comma; treating cultured neurons with
RNAi targeting alpha-takusan variants resulted in the opposite phenotype.
Hence&s_comma; alpha-takusan represents a novel gene family that regulates synaptic