Angiotensin-Receptor-Associated Protein Modulates Ca(2+) Signals in Photoreceptor and Mossy Fiber cells

Fast, precise and sustained neurotransmission requires graded Ca(2+) signals at the presynaptic terminal. Neurotransmitter release depends on a complex interplay of Ca(2+) fluxes and Ca(2+) buffering in the presynaptic terminal that is not fully understood. Here, we show that the angiotensin-receptor-associated protein (ATRAP) localizes to synaptic terminals throughout the central nervous system. In the retinal photoreceptor synapse and the cerebellar mossy fiber-granule cell synapse, we find that ATRAP is involved in the generation of depolarization-evoked synaptic Ca(2+) transients. Compared to wild type, Ca(2+) imaging in acutely isolated preparations of the retina and the cerebellum from ATRAP knockout mice reveals a significant reduction of the sarcoendoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA) activity. Thus, in addition to its conventional role in angiotensin signaling, ATRAP also modulates presynaptic Ca(2+) signaling within the central nervous system.