FIGURE 3.

Signaling by kinases and phosphatases in postsynaptic excitation-transcription coupling. Anchored kinases and phosphatases finely tune Ca²⁺ influx through LTCCs. The calcium-activated phosphatase CaN dephosphorylates nuclear localization sequences on the transcription factors NFAT and CRTC1, permitting their translocation to the nucleus. LTCC-calcium influx also activates CaMKIIα/β that can phosphorylate and “lock” CaMKIIγ in a conformation that tightly binds Ca²⁺-CaM. Subsequent CaN-mediated dephosphorylation of the nuclear localization sequence of CaMKIIγ drives nuclear translocation and delivery of Ca²⁺-CaM to CaMKIV, which phosphorylates and actives CREB. Green lines represent phosphorylation, and red lines represent dephosphorylation.