Fig. 2

Simplified diagram of IEG signalling pathways. NMDAR-mediated Ca²⁺ influx leads to activation of signalling pathways transporting the signal to the nucleus. MAPK pathway-activated protein kinases phosphorylate CREB and ELK-1 transcription factors that bind regulatory elements of the immediate early genes. Arc and Homer mRNA is transported to the synapse, where it is translated. ARC downregulates AMPAR by interacting with endophilin and dynamin and enhancing the receptor endocytosis. Homer 1a selectively binds group 1 metabotropic receptors, thus, it competes with constitutively expressed CC-Homers and disassembles the signaling complex, inactivating mGluR. The c-FOS and ZIF268 proteins are transported back into the nucleus, after translation in the cytoplasm. Inside the nucleus, downstream gene transcription is regulated by ZIF268 and AP-1 complex, which is a dimer of c-FOS and c-JUN