Serotonin induces selective cleavage of the PKA RI subunit but not RII subunit in Aplysia neurons.
PKA type I and type II are activated in Aplysia neurons by stimulation with serotonin (5-HT), which causes long-term facilitation (LTF). The proteolysis of the regulatory subunit (R) is thought important for the persistent activation of PKA, which is necessary to produce LTF. In this study, we report that the type I regulatory subunit (RI) and type II regulatory subunit (RII) are differentially regulated by proteolytic cleavage. RI, but not RII, was selectively cleaved after 5-HT treatment for 2h in Aplysia neurons. Interestingly, the proteasome inhibitor MG132 inhibited the cleavage of RI caused by 5-HT treatment in Aplysia neuron. Besides extracts from Aplysia ganglia treated with 5-HT cleaved (35)S-labeled RI synthesized in vitro, but not (35)S-labeled RII. This suggests that 5-HT induces the activation state of RI-specific proteolytic cleavage.
Kurosu
Takeshi
T
Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York State Psychiatric Institute, New York, NY 10032, USA. tkurosu@biken.osaka-u.ac.jp
Hernández
A Iván
AI
Schwartz
James H
JH
D000818:Animals; D001048:Aplysia / Q000187:drug effects* / Q000201:enzymology*; D002457:Cell Extracts; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology*; D010766:Phosphorylation; D021122:Protein Subunits / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism
D002457:Cell Extracts; D017362:Cyclic AMP Response Element-Binding Protein; D021122:Protein Subunits; D014404:Tubulin; D012701:Serotonin; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases