Question

PKA has always been considered important information of a memory. Long term memory is dependent on the CREB transcription factor, which is regulated by PKA. When PKA phosphorylates CREB, CREB will transcribe genes involved in long term memory formation. Which of the following would lead to a decrease in memory formation? addition of a drug that activates adenylyl cyclase addition of a drug that prevents GTP hydrolysis by Ga addition of a drug that causes cyclic AMP phosphodiesterase to be inactive addition of a drug that prevents the regulatory subunit from coming off of PKA

Answer 1

The correct option will be the 4th one, that is, addition of a drug that prevents the regulatory subunit from coming off of PKA

The functioning of PKA occurs through GPCR signaling pathway. Activation of GPCR through ligand binding activates a G-protein. G-protein remains activated in the GTP bound state (whereas, GTP hydrolysis inactivates the G-protein). Activated G-protein mediates dissociation of G-alpha subunit. Dissociated G-alpha then activates adenylyl cyclase enzyme, which produces cAMP from ATP. Another enzyme, called cyclic AMP phosphodiesterase, functions to convert cAMP back to ATP, thus, activation of this enzyme will stop the signaling pathway. cAMP in turn activates protein kinase A or PKA.

PKA is a tetramer, consisting of two regulatory and two catalytic subunits. The activation of PKA occurs through the binding of cAMP to the regulatory subunits, which causes them to separate from the catalytic subunits. Dissociation of catalytic subunits from the regulatory subunits activates PKA. Active PKA is responsible for phosphorylating it's targets, one of which is CREB. Phosphorylated CREB then transcribes genes involved in long term memory formation. Thus, separation of regulatory subunits of PKA from the catalytic subunits is important for inducing long term memory. Preventing the separation process will lead to decreased memory formation.