Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 9, Pages 3531-3536Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0813263106
Keywords
dopamine; medium spiny neuron; cAMP; PKA; EPAC
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Funding
- NIDA NIH HHS [DA11717, P01 DA010044, R01 DA011717, DA10044] Funding Source: Medline
- NIMH NIH HHS [MH74866, P50 MH074866] Funding Source: Medline
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Protein kinase A (PKA)-dependent signaling cascades play an important role in mediating the effects of dopamine and other neurotransmitters in striatal medium spiny neurons. We have identified a prominent striatal PKA substrate as Rap1-GTPase activating protein (Rap1GAP), a negative regulator of Rap1 signaling. Although present throughout the brain, Rap1GAP is enriched in striatal medium spiny neurons and is phosphorylated by PKA at Ser-441 and Ser-499 in response to activation of D1 dopamine receptors. Phosphorylation of Rap1GAP is associated with inhibition of GAP activity, as demonstrated by increased Rap1 activity in striatal neurons. Phosphorylation of Rap1GAP is also associated with increased dendritic spine head size in cultured neurons. These findings suggest that phosphorylation of Rap1GAP by PKA plays an important role in striatal neurons by modulating Rap1 actions.
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