Model for FMRP and Fmr1 mRNA localization in dendrites and at synapses. Glutamatergic stimulation activates the mGluR, triggering release of internal calcium and activation of PKC, a cascade of events that localizes FMRP and Fmr1 mRNA in dendrites. FMRP and its target mRNA colocalize at the synapse, in a complex where FMRP represses translation. Synaptic activation causes the dissociation of FMRP from the target mRNA, relieving the repression, and the loss of FMRP from the synapse, perhaps because of PKC phosphorylation. Although there is no direct evidence that PKC phosphorylates FMRP, it is known that there is a phosphorylation site on the FMRP protein (Ceman et al., 2003). Phosphorylated FMRP could become a retrograde messenger, returning to the cell body. Meanwhile, the mRNA is now derepressed and able to translate proteins that are important for synaptic structure and plasticity.