RGD Reference Report - Direct association of the unique C-terminal tail of transmembrane AMPA receptor regulatory protein gamma-8 with calcineurin. - Rat Genome Database

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Direct association of the unique C-terminal tail of transmembrane AMPA receptor regulatory protein gamma-8 with calcineurin.

Authors: Itakura, M  Watanabe, I  Sugaya, T  Takahashi, M 
Citation: Itakura M, etal., FEBS J. 2014 Mar;281(5):1366-78. doi: 10.1111/febs.12708. Epub 2014 Jan 27.
RGD ID: 8553314
Pubmed: PMID:24418105   (View Abstract at PubMed)
DOI: DOI:10.1111/febs.12708   (Journal Full-text)

Transmembrane alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor regulatory proteins (TARPs) are auxiliary subunits that regulate AMPA receptor trafficking to the plasma membrane and localization to postsynaptic sites. The classical TARP family consists of four members: stargazin/gamma-2, gamma-3, gamma-4 and gamma-8. The TARP gamma-8 isoform, which is highly expressed in the hippocampus, has a unique, long C-terminal domain with five distinct regions: two glycine-rich regions, a serine/arginine-rich region, a proline/alanine (P/A) rich region, and a PSD-95/Dlg/ZO-1 (PDZ) binding motif. We performed mass spectrometry and immunoprecipitation assays to identify specific binding partners for the gamma-8 C-terminal tail and found that gamma-8, but not stargazin/gamma-2, co-immunoprecipitated with calcineurin/PP2B, a Ca(2+) /calmodulin-dependent Ser/Thr phosphatase. Co-immunoprecipitation and immunoblot analyses of lysates from COS-7 cells co-transfected with calcineurin and either wild type or chimeric gamma-8 revealed that a section of the C-terminal tail (residues 356-421) can bind calcineurin. Futhermore, gamma-8 lacking the P/A-rich region (residues 383-399) did not bind to calcineurin. In addition, the GST-gamma-8 C-terminal tail (residues 353-414) fusion protein containing the P/A-rich region bound to purified calcineurin in a Ca(2+) /calmodulin-dependent manner, whereas GST-gamma-8 with a deletion of the P/A-rich region did not. Peptide competition assays demonstrated that gamma-8 may interact with the hydrophobic pocket defined by beta-sheet 14 and/or adjacent regions of the catalytic A subunit of calcineurin. These results indicate that the gamma-8 P/A-rich region is essential for binding calcineurin, suggesting that the gamma-8/calcineurin complex may regulate AMPA receptor phosphorylation and trafficking.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dendrite membrane  IDA 8553314 RGD 
postsynaptic membrane  IDA 8553314 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cacng2  (calcium voltage-gated channel auxiliary subunit gamma 2)
Cacng8  (calcium voltage-gated channel auxiliary subunit gamma 8)
Dlg4  (discs large MAGUK scaffold protein 4)
Gria1  (glutamate ionotropic receptor AMPA type subunit 1)
Gria2  (glutamate ionotropic receptor AMPA type subunit 2)
Ppp3ca  (protein phosphatase 3 catalytic subunit alpha)
Ppp3cb  (protein phosphatase 3 catalytic subunit beta)


Additional Information