Synaptic transmission relies on rapid calcium (Ca2+) influx into presynaptic terminal via voltage-gated Ca2+ channels. However, smooth ER is present in presynaptic terminals and accumulating evidence indicate that ER Ca2+ signaling may play a modulatory role in synaptic transmission. Most recent publication by Lindhout and colleagues (EMBO J, 38 (2019) e101345) suggested that the fragmentation state of the ER affects synaptic vesicle release. Here we discuss these results as well as several key publications that addressed a connection between ER Ca2+ signaling and synaptic transmission.
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