p97 regulates GluA1 homomeric AMPA receptor formation and plasma membrane expression.

Titlep97 regulates GluA1 homomeric AMPA receptor formation and plasma membrane expression.
Publication TypeJournal Article
Year of Publication2019
AuthorsGe Y, Tian M, Liu L, Wong TPan, Gong B, Wu D, Cho T, Lin S, Kast J, Lu J, Wang YTian
JournalNat Commun
Volume10
Issue1
Pagination4089
Date Published2019 Sep 09
ISSN2041-1723
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.

DOI10.1038/s41467-019-12096-7
Alternate JournalNat Commun
PubMed ID31501443
PubMed Central IDPMC6733861
Grant ListM0P-38090 / / Gouvernement du Canada | Instituts de Recherche en Santé du Canada | CIHR Skin Research Training Centre (Skin Research Training Centre) /
FDN-154286 / / Gouvernement du Canada | Instituts de Recherche en Santé du Canada | CIHR Skin Research Training Centre (Skin Research Training Centre) /