TY - JOUR
T1 - AMPA receptors in the synapse turnover by monomer diffusion
AU - Morise, Jyoji
AU - Suzuki, Kenichi G.N.
AU - Kitagawa, Ayaka
AU - Wakazono, Yoshihiko
AU - Takamiya, Kogo
AU - Tsunoyama, Taka A.
AU - Nemoto, Yuri L.
AU - Takematsu, Hiromu
AU - Kusumi, Akihiro
AU - Oka, Shogo
N1 - Funding Information:
We thank Prof. Richard L. Huganir of Johns Hopkins University for the gift of the mouse GluA1 mAb, Prof. Masayoshi Mishina of Ritsumeikan University for the gift of the cDNAs encoding GluA1 and GluA2, Prof. Yoshiaki Tagawa of Kagoshima University and Prof. Tomoo Hirano of Kyoto University for the gift of the cDNA encoding Homer1b-EGFP, and Dr. Eric J. Brown of Genentech for the gift of the cDNA encoding CD47. This work was supported in part by Grants-in-Aid for scientific research from the Japan Society for the Promotion of Science (Young Scientists (B) [17K15090, 19K16074] to J.M., Kiban B to K.G.N.S. [15H04351, 18H02401] and to S.O. [19H03370], Challenging Exploratory Research [16K14695] to S.O. and [17K19521] to K.G.N.S., and Kiban A and S to A.K. [24247029 and 16H06386, respectively]), Grants-in-Aid for Innovative Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan to S.O. (23110006) and K.G.N.S. (23110001, 18H04671), and a grant from the Core Research for Evolutional Science and Technology project of “Creation of Fundamental Technologies for Understanding and Control of Biosystem Dynamics” of Japan Science and Technology Agency to A.K. WPI-iCeMS of Kyoto University is supported by the World Premiere Research Center Initiative of the MEXT.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - The number and subunit compositions of AMPA receptors (AMPARs), hetero- or homotetramers composed of four subunits GluA1–4, in the synapse is carefully tuned to sustain basic synaptic activity. This enables stimulation-induced synaptic plasticity, which is central to learning and memory. The AMPAR tetramers have been widely believed to be stable from their formation in the endoplasmic reticulum until their proteolytic decomposition. However, by observing GluA1 and GluA2 at the level of single molecules, we find that the homo- and heterotetramers are metastable, instantaneously falling apart into monomers, dimers, or trimers (in 100 and 200 ms, respectively), which readily form tetramers again. In the dendritic plasma membrane, GluA1 and GluA2 monomers and dimers are far more mobile than tetramers and enter and exit from the synaptic regions. We conclude that AMPAR turnover by lateral diffusion, essential for sustaining synaptic function, is largely done by monomers of AMPAR subunits, rather than preformed tetramers.
AB - The number and subunit compositions of AMPA receptors (AMPARs), hetero- or homotetramers composed of four subunits GluA1–4, in the synapse is carefully tuned to sustain basic synaptic activity. This enables stimulation-induced synaptic plasticity, which is central to learning and memory. The AMPAR tetramers have been widely believed to be stable from their formation in the endoplasmic reticulum until their proteolytic decomposition. However, by observing GluA1 and GluA2 at the level of single molecules, we find that the homo- and heterotetramers are metastable, instantaneously falling apart into monomers, dimers, or trimers (in 100 and 200 ms, respectively), which readily form tetramers again. In the dendritic plasma membrane, GluA1 and GluA2 monomers and dimers are far more mobile than tetramers and enter and exit from the synaptic regions. We conclude that AMPAR turnover by lateral diffusion, essential for sustaining synaptic function, is largely done by monomers of AMPAR subunits, rather than preformed tetramers.
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U2 - 10.1038/s41467-019-13229-8
DO - 10.1038/s41467-019-13229-8
M3 - Article
C2 - 31748519
AN - SCOPUS:85075402331
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 5245
ER -