Wei_2023_Prog.Neurobiol__102559

Reference

Title : ABHD6 drives endocytosis of AMPA receptors to regulate synaptic plasticity and learning flexibility - Wei_2023_Prog.Neurobiol__102559
Author(s) : Wei M , Yang L , Su F , Liu Y , Zhao X , Luo L , Sun X , Liu S , Dong Z , Zhang Y , Shi YS , Liang J , Zhang C
Ref : Prog Neurobiol , :102559 , 2023
Abstract :

Trafficking of alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors (AMPARs), mediated by AMPAR interacting proteins, enabled neurons to maintain tuning capabilities at rest or active state. alpha/beta-Hydrolase domain-containing 6 (ABHD6), an endocannabinoid hydrolase, was an AMPAR auxiliary subunit found to negatively regulate the surface delivery of AMPARs. While ABHD6 was found to prevent AMPAR tetramerization in endoplasmic reticulum, ABHD6 was also reported to localize at postsynaptic site. Yet, the role of ABHD6 interacting with AMPAR at postsynaptic site, and the physiological significance of ABHD6 regulating AMPAR trafficking remains elusive. Here, we generated the ABHD6 knockout (ABHD6(KO)) mice and found that deletion of ABHD6 selectively enhanced AMPAR-mediated basal synaptic responses and the surface expression of postsynaptic AMPARs. Furthermore, we found that loss of ABHD6 impaired hippocampal long-term depression (LTD) and synaptic downscaling in hippocampal synapses. AMPAR internalization assays revealed that ABHD6 was essential for neuronal activity-dependent endocytosis of surface AMPARs, which is independent of ABHD6's hydrolase activity. The defects of AMPAR endocytosis and LTD are expressed as deficits in learning flexibility in ABHD6(KO) mice. Collectively, we demonstrated that ABHD6 is an endocytic accessory protein promoting AMPAR endocytosis, thereby contributes to the formation of LTD, synaptic downscaling and reversal learning.

PubMedSearch : Wei_2023_Prog.Neurobiol__102559
PubMedID: 38159878
Gene_locus related to this paper: human-ABHD6 , mouse-ABHD6

Related information

Gene_locus human-ABHD6    mouse-ABHD6
Family human-ABHD6    mouse-ABHD6    ABHD6-Lip

Citations formats

Wei M, Yang L, Su F, Liu Y, Zhao X, Luo L, Sun X, Liu S, Dong Z, Zhang Y, Shi YS, Liang J, Zhang C (2023)
ABHD6 drives endocytosis of AMPA receptors to regulate synaptic plasticity and learning flexibility
Prog Neurobiol :102559

Wei M, Yang L, Su F, Liu Y, Zhao X, Luo L, Sun X, Liu S, Dong Z, Zhang Y, Shi YS, Liang J, Zhang C (2023)
Prog Neurobiol :102559