RAP2A/A0033

Ras-related protein 2A, also known as RAP2A or A0033, belongs to the class of G proteins and has been shown to be important in the regulation of both long-term potentiation (LTP) and LDP.

Ras-related protein 2A, also known as RAP2A or A0033, belongs to the class of G proteins and has been shown to be important in the regulation of both long-term potentiation (LTP) and LDP. It is expressed in the post-synaptic proteome and N-methyl-D-aspartate (NMDA) receptor complex synaptic proteomes, yet is not found in the post-synaptic density (PSD) complement. The protein has a guanosine triphosphate (GTP)-binding domain, a Ras-like C-terminal motif for post-translational lipid modification (perhaps, this limits both the nature and number of interactions it can form with other proteins in the proteomic complement) for subsequent anchoring to plasma membrane. Site-directed mutagenesis studies have shown that glycine 12 and threonine 35 are involved in GTPase activity, whilst threonine 145 appears to be involved in guanyl nucleotide binding. Serine 17 appears to coordinate the magnesium ions, which are essential for its function. It has been observed that RAP2A is expressed at excitatory synapses in the rodent brain and a functional RAP2A signaling pathway has been identified in cultured mouse hippocampal CA1 neurons. Indeed, both synaptic activity and activation of NR2A-containing NMDA receptor complexes can activate RAP2A activity, which can then sequentially up-regulate C-Jun N-terminal kinase (JNK). Both the abovementioned effects are essential for depolarization and can cause the removal of Glur1 and Glur2–containing alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor complexes. It has also been further shown that Rap2a appears to perform a dual regulatory role in the coordination of LTP and LTD levels: it complement LTD induced by Rap1 signaling ; concomitantly, it opposes LTP induced by Ras signaling. Further studies could help illuminate the integral, if not computational relationship, between LTD and LTP and their cross-regulation, for evolutionarily speaking, it would be beneficial to coordinate these two activities, so that they are in sync and happen in an efficient manner, relative to one another.