Activity-Dependent Localization and Heterogeneous Dynamics of STIM1 and STIM2 at ER-PM contacts in Hippocampal Neurons

Abstract

Stromal interaction molecules (STIMs) are calcium sensors integral to store-operated calcium entry (SOCE), a process critical for non-excitable cells and contributing to homeostatic functions in neurons. Upon depletion of Ca2+ from the endoplasmic reticulum (ER), STIMs translocate to ER-plasma membrane (PM) junctions to contact the inner leaflet of the plasma membrane. Using single-particle tracking (SPT), we characterized the dynamic properties of neuronal STIM1 and STIM2 in hippocampal neurons. Our data reveal that STIMs exhibit heterogenous dynamics in dendrites and axons, while only transiently visiting synaptic compartments. A substantial fraction of STIM2 proteins define ER-PM contacts under resting conditions, STIM1 proteins are recruited to ER-PM junctions during strong activation of glutamatergic synapses. Junctions organized by KV2.1 channels are not particularly enriched with STIM proteins. Activity dependent confinement of STIM proteins is not influenced by L-type calcium channel (Cav1.2) activity. We propose that STIM proteins predominantly regulate the contact area and frequency of contacts between ER and PM.