p97 regulates GluA1 homomeric AMPA receptor formation and plasma membrane expression

Yuan Ge (), Meng Tian, Lidong Liu, Tak Pan Wong, Bo Gong, Dongchuan Wu, Taesup Cho, Shujun Lin, Jürgen Kast, Jie Lu () and Yu Tian Wang ()
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Yuan Ge: University of British Columbia
Meng Tian: University of British Columbia
Lidong Liu: University of British Columbia
Tak Pan Wong: University of British Columbia
Bo Gong: University of British Columbia
Dongchuan Wu: University of British Columbia
Taesup Cho: University of British Columbia
Shujun Lin: University of British Columbia
Jürgen Kast: University of British Columbia
Jie Lu: University of British Columbia
Yu Tian Wang: University of British Columbia

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate receptors (AMPARs) mediate the fast excitatory synaptic transmission in the mammalian brain and are important for synaptic plasticity. In particular, the rapid insertion of the GluA1 homomeric (GluA1-homo) AMPARs into the postsynaptic membrane is considered to be critical in the expression of hippocampal CA1 long-term potentiation (LTP), which is important for certain forms of learning and memory. However, how the formation and trafficking of GluA1-homo AMPARs are regulated remains poorly understood. Here, we report that p97 specifically interacts with and promotes the formation of GluA1-homo AMPARs. The association with p97 retains GluA1-homo AMPARs in the intracellular compartment under basal conditions, and its dissociation allows GluA1-homo AMPARs to be rapidly inserted into the postsynaptic membrane shortly after LTP induction. Thus, our results shed lights into the molecular mechanisms by which p97 regulates GluA1-homo AMPARs formation and trafficking, thereby playing a critical role in mediating synaptic plasticity.

Date: 2019
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DOI: 10.1038/s41467-019-12096-7

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