Mechanisms for AMPA-type glutamate receptor anchoring at the synapse

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04279
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: FUKATA Yuko 生理学研究所, 分子細胞生理研究領域, 准教授 (40416186)
• Research Collaborator: YOKOI Norihiko 生理学研究所, 分子細胞生理研究領域, 助教 (50710969) ; HIRATA Tetsuya 生理学研究所, 分子細胞生理研究領域, 特任助教 (90780651) ; TAKAHASHI Naoki ; INAHASHI Hiroki ; SEKIYA Atsushi ; MURAKAMI Tatsuro ; FURUKAWA Sachiko ; SUZUKI Yumi
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: シナプス / AMPA受容体 / グルタミン酸受容体 / パルミトイル化脂質修飾 / PSD-95 / てんかん / 脱パルミトイル化 / ナノドメイン

Outline of Final Research Achievements

AMPA-type glutamate receptor (AMPAR) mediates most of fast synaptic transmission in the brain. Although AMPAR dynamically enters and exits the postsynaptic membrane in a synaptic activity-dependent manner, the underlying molecular mechanism is still incompletely understood. In this study, we focused on palmitoylation and protein-protein interactions of PSD-95, an essential scaffolding protein for AMPAR. We discovered a novel enzyme, ABHD17, which catalyzes PSD-95 depalmitoylation and thereby plays an important role in the (re)organization of the postsynaptic platform for AMPAR anchoring. We also found that the epilepsy-related ligand/receptor complex of LGI1 and ADAM22 regulates AMPAR functions through the direct interaction with PSD-95. Furthermore, we revealed the structural basis of the LGI1-ADAM22 protein complex at the synapse and its patho-physiological role in epileptogenesis.

Free Research Field

神経科学、細胞生物学、生化学