Presynaptic endoplasmic reticulum and neurotransmission

Abstract

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.

Fig. 1.. Presynaptic ER Ca²⁺ stores.

Presynaptic terminal is filled with synaptic vesicles (SVs). Canonical evoked neurotransmission is driven by Ca²⁺ influx through voltage gated Ca²⁺ channels (VGCCs). Smooth ER is present in many presynpatic terminals. Ca²⁺ release from ER is mediated by ryanodine receptors (RyR) by a mechanism of Ca²⁺-induced Ca²⁺ release (CICR). ER Ca²⁺ depletion causes clustering of STIM1 Ca²⁺ sensor protein and activation of store-operated Ca²⁺ entry pathway (SOCE) via Ca²⁺ influx through Orai channels. There is increasing evidence that both CICR and SOCE can impact neurotransmitter release.