Figure 1

XBP1 signaling and neuronal plasticity. Presynaptic influx of Ca²⁺ releases glutamate into the synaptic cleft. This activates AMPA, EphB2 and NMDA receptors at the postsynaptic membrane that engages CaMKs and induces the transcription of the Bdnf gene. In parallel, XBP1 can be locally synthetized within dendrites through SPRCs and transported into the nucleus to activate transcription of BDNF, Kalirin-7 and a myriad of other genes that are crucial for the survival and plasticity of neurons. mBDNF is released at synapses and activates TrkB receptors to recruit XBP1 and Kalirin-7, which controls spinogenesis through Rho-GTPases RAC1 and PAK1, resulting in a positive activation loop. BDNF signaling also regulates synaptic transmission through control of neurotransmitter release at presynaptic terminals. Abbreviations: AMPA(R), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (receptor); BDNF, brain-derived neurotrophic factor; CaMK, Ca²⁺/calmodulin-dependent kinase; NMDA(R), N-methyl-D-aspartate (receptor); SPRCs, synapse-associated polyribosome complexes; EphB2, EphrinB2 receptor. Whether EphB2 acts upstream of XBP1 remains to be determined. Graphic adapted from (235).