Abundant distribution of TARP γ-8 in synaptic and extrasynaptic surface of hippocampal neurons and its major role in AMPA receptor expression on spines and dendrites

Fukaya, Masahiro; Tsujita, Mika; Yamazaki, Maya; Kushiya, Etsuko; Abe, Manabu; Akashi, Kaori; Natsume, Rie; Kano, Masanobu; Kamiya, Haruyuki; Watanabe, Masahiko; Sakimura, Kenji

Abundant distribution of TARP γ-8 in synaptic and extrasynaptic surface of hippocampal neurons and its major role in AMPA receptor expression on spines and dendrites

Fukaya, Masahiro; Tsujita, Mika; Yamazaki, Maya et al.

European Journal of Neuroscience, 2006, 24(8), 2177-2190

Permalink : https://hdl.handle.net/2115/30133

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アクセス権	open access
URI	https://hdl.handle.net/2115/30133
タイトル	Abundant distribution of TARP γ-8 in synaptic and extrasynaptic surface of hippocampal neurons and its major role in AMPA receptor expression on spines and dendrites
著者	Fukaya, Masahiro ; Tsujita, Mika ; Yamazaki, Maya ; Kushiya, Etsuko ; Abe, Manabu ; Akashi, Kaori ; Natsume, Rie ; Kano, Masanobu ; Kamiya, Haruyuki ; Watanabe, Masahiko ; Sakimura, Kenji
著者名 Fukaya, Masahiro
著者名 Tsujita, Mika
著者名 Yamazaki, Maya
著者名 Kushiya, Etsuko
著者名 Abe, Manabu
著者名 Akashi, Kaori
著者名 Natsume, Rie
著者名 Kano, Masanobu
著者名 Kamiya, Haruyuki
e-Rad_Researcher 70210945 著者名 Watanabe, Masahiko
著者名 Sakimura, Kenji
言語	英語
キーワード	Hippocampus
	pyramidal cell
	transmembrane AMPA receptor regulatory protein
	immunohistochemistry
	immunoblot
発行日	2006-10
出版者	Blackwell Publishing
収録物名	European Journal of Neuroscience
巻(号)	24(8)
ページ	2177-2190
抄録	Transmembrane AMPA receptor regulatory proteins (TARPs) play pivotal roles in AMP A receptor trafficking and gating. Here we examined cellular and subcellular distribution of TARP γ-8 in the mouse brain. Immunoblot and immunofluorescence revealed the highest concentration of γ-8 in the hippocampus. Immunogold electron microscopy demonstrated dense distribution of γ-8 on the synaptic and extrasynaptic surface of hippocampal neurons with very low intracellular labeling. Of the neuronal surface, γ-8 was distributed at the highest level on asymmetrical synapses of pyramidal cells and interneurons, whereas their asymmetrical synapses selectively lacked immunogold labeling. Then, the role of γ-8 in AMPA receptor expression was pursued in the hippocampus using mutant mice defective in the γ-8 gene. In the mutant CA1 region, synaptic and extrasynaptic AMPA receptors on dendrites and spines were severely reduced to 35-37% of control levels, whereas reduction was mild for extrasynaptic receptors on somata (74%) and no significant decrease was seen for intracellular receptors within spines. In the mutant CA3 region, synaptic AMPA receptors were reduced mildly at asymmetrical synapses in the stratum radiatum (67% of control level), and showed no significant decrease at mossy fiber-CA3 synapses. Therefore, γ-8 is abundantly distributed on hippocampal excitatory synapses and extrasynaptic membranes, and plays an important role in increasing the number of synaptic and extrasynaptic AMPA receptors on dendrites and spines, particularly, in the CA1 region. Variable degrees of reduction further suggest that other TARPs may also mediate this function at different potencies depending on hippocampal subregions, input sources, and neuronal compartments.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	The definitive version is available at www.blackwell-synergy.com
PISSN	0953-816X
EISSN	1460-9568
関連情報	PMID 17074043
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1111/j.1460-9568.2006.05081.x