title: The type II cGMP dependent protein kinase regulates GluA1 levels at the plasma membrane of developing cerebellar granule cells.
abstract: Trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is regulated by specific interactions with other proteins and by post-translational mechanisms, such as phosphorylation. We have found that the type II cGMP-dependent protein kinase (cGKII) phosphorylates GluA1 (formerly GluR1) at S845, augmenting the surface expression of AMPARs at both synaptic and extrasynaptic sites. Activation of cGKII by 8-Br-cGMP enhances the surface expression of GluA1, whereas its inhibition or suppression effectively diminished the expression of this protein at the cell surface. In granule cells, NMDA receptor activation (NMDAR) stimulates nitric oxide and cGMP production, which in turn activates cGKII and induces the phosphorylation of GluA1, promoting its accumulation in the plasma membrane. GluA1 is mainly incorporated into calcium permeable AMPARs as exposure to 8-Br-cGMP or NMDA activation enhanced AMPA-elicited calcium responses that are sensitive to NASPM inhibition. We summarize evidence for an increase of calcium permeable AMPA receptors downstream of NMDA receptor activation that might be relevant for granule cell development and plasticity.
authors.affiliation: Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, Madrid, Spain.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Incontro
authors.forename: Francisco
authors.initials: F
authors.lastname: Ciruela
authors.forename: Edward
authors.initials: E
authors.lastname: Ziff
authors.forename: Franz
authors.initials: F
authors.lastname: Hofmann
authors.forename: José
authors.initials: J
authors.lastname: Sánchez-Prieto
authors.forename: Magdalena
authors.initials: M
authors.lastname: Torres
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000201:enzymology / Q000378:metabolism*; D006152:Cyclic GMP / Q000235:genetics / Q000378:metabolism; D062967:Cyclic GMP-Dependent Protein Kinase Type II / Q000235:genetics / Q000378:metabolism*; D005260:Female; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism
chemical_list: D002118:Calcium; D006152:Cyclic GMP; D062967:Cyclic GMP-Dependent Protein Kinase Type II; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate
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