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Regulation of GluA1 AMPA Receptor Through PKC Phosphorylation Induced by Free Fatty Acid Derivative HUHS2002
Author(s) -
Nishimoto Takaaki,
Kanno Takeshi,
Shimizu Tadashi,
Tanaka Akito,
Nishizaki Tomoyuki
Publication year - 2013
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-012-3736-4
Subject(s) - ampa receptor , protein kinase c , chemistry , receptor , phosphorylation , long term potentiation , microbiology and biotechnology , kinase , biochemistry , glutamate receptor , biology
The present study investigated the effect of 4‐[4‐( Z )‐hept‐1‐enyl‐phenoxy] butyric acid (HUHS2002), a newly synthesized free fatty acid derivative, on α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptor responses. HUHS2002 potentiated currents through GluA1 AMPA receptors expressed in Xenopus oocytes in a bell‐shaped concentration (1 nM–1 μM)‐dependent manner, the maximum reaching nearly 140 % of original amplitude at 100 nM. The potentiation was significantly inhibited by GF109203X, an inhibitor of protein kinase C (PKC), but not KN‐93, an inhibitor of Ca 2+ /calmodulin‐dependent protein kinase II (CaMKII). HUHS2002 had no potentiating effect on currents through mutant GluA1 AMPA receptors with replacement of Ser831, a PKC/CaMKII phosphorylation site, by Ala. In the in situ PKC assay using rat PC‐12 cells, HUHS2002 significantly enhanced PKC activity, that is suppressed by GF109203X. Overall, the results of the present study show that HUHS2002 potentiates GluA1 AMPA receptor responses by activating PKC and phosphorylating the receptors at Ser831, regardless of CaMKII activation and phosphorylation.