M.F. and M.T. contributed equally to this work.
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
Article first published online: 24 OCT 2006
European Journal of Neuroscience
Volume 24, Issue 8, pages 2177–2190, October 2006
How to Cite
Fukaya, M., Tsujita, M., Yamazaki, M., Kushiya, E., Abe, M., Akashi, K., Natsume, R., Kano, M., Kamiya, H., Watanabe, M. and Sakimura, K. (2006), 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. European Journal of Neuroscience, 24: 2177–2190. doi: 10.1111/j.1460-9568.2006.05081.x
- Issue published online: 24 OCT 2006
- Article first published online: 24 OCT 2006
- Received 13 May 2006, revised 24 July 2006, accepted 29 July 2006
- pyramidal cell;
- transmembrane AMPA receptor regulatory protein
Transmembrane α-amino-3-hydroxyl-5-isoxazolepropionate (AMPA) receptor regulatory proteins (TARPs) play pivotal roles in AMPA 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 symmetrical 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 cornu ammonis (CA)1 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.