A short isoform of STIM1 confers frequency-dependent synaptic enhancement

• DOI: 10.1016/j.celrep.2021.108844
• Publication Date: 2021-03-18T21:16:23Z
• Authors: Girish Ramesh; Lukas Jarzembowski; Yvonne Schwarz; Vanessa Poth; Maik Konrad; Mona L. Knapp; Gertrud Schwär; Anna A. Lauer; Marcus O.W. Grimm; Dalia Alansary; Dieter Bruns; Barbara A. Niemeyer
• Keywords: Calcium Signaling; Homeostasis

Store-operated Ca2+-entry (SOCE) regulates basal and receptor-triggered Ca2+ signaling with STIM proteins sensing the endoplasmic reticulum (ER) content triggering entry by gating Orai channels. Although crucial for immune cells, STIM1's role in neuronal homeostasis is controversial. Here, we characterize a splice variant, STIM1B, which shows exclusive expression protein surpassing conventional STIM1 cerebellum of significant abundance other brain regions. STIM1B results truncated slower kinetics ER-plasma membrane (PM) cluster formation ICRAC, as well reduced inactivation. In primary wild-type neurons, targeted its spliced-in domain B to presynaptic sites where it converts classic synaptic depression into Ca2+- Orai-dependent short-term enhancement (STE) at high-frequency stimulation (HFS). conjunction altered splicing human Alzheimer disease, our findings highlight an important regulator calcium plasticity.