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Short Novel STIM1B Uncovers a Mechanism of Synaptic Enhancement

53 Pages Posted: 21 Oct 2020 Publication Status: Published

See all articles by Girish Ramesh

Girish Ramesh

Saarland University - Molecular Biophysics

Lukas Jarzembowksi

Saarland University - Molecular Biophysics

Yvonne Schwarz

Saarland University - Molecular Neurophysiology

Maik Konrad

Saarland University - Molecular Biophysics

Vanessa Poth

Saarland University - Molecular Biophysics

Gertrud Schwaer

Saarland University - Biophysics

Anna A. Lauer

Saarland University - Experimental Neurology

Marcus O.W. Grimm

Saarland University - Experimental Neurology

Dalia Alansary

Saarland University - Molecular Biophysics

Dieter Bruns

Saarland University - Molecular Neurophysiology

Barbara Anne Niemeyer

Saarland University - Center for Integrative Physiology and Molecular Medicine (CIPMM)

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Abstract

Store-operated Ca2+-entry (SOCE) regulates basal and receptor-triggered Ca2+ signaling with STIM proteins sensing the endoplasmic reticulum (ER) Ca2+ content and triggering Ca2+ entry by gating Orai channels. Although crucial for immune cells, STIM1’s role in neuronal Ca2+ homeostasis is controversial. Here, we characterize a novel splice variant, STIM1B, with exclusive neuronal expression, protein content surpassing conventional STIM1 in cerebellum and significant abundance in hippocampus. STIM1B results in a truncated protein with slower kinetics of ER-PM cluster formation and ICRAC as well as reduced inactivation. In primary wild-type neurons, Stim1B is targeted by its spliced-in domain B to presynaptic sites where it converts classic synaptic depression into Ca2+- and Orai-dependent short-term synaptic enhancement (STE) at high frequency stimulation (HFS). In conjunction with altered STIM1 splicing in human Alzheimer disease, our findings highlight STIM1 splicing as an important regulator of neuronal calcium homeostasis and synaptic plasticity.

Keywords: Orai, SOCE, ICRAC, vesicles, endocytosis, short term enhancement, presynaptic ER, Alzheimer

Suggested Citation

Ramesh, Girish and Jarzembowksi, Lukas and Schwarz, Yvonne and Konrad, Maik and Poth, Vanessa and Schwaer, Gertrud and Lauer, Anna A. and Grimm, Marcus O.W. and Alansary, Dalia and Bruns, Dieter and Niemeyer, Barbara Anne, Short Novel STIM1B Uncovers a Mechanism of Synaptic Enhancement. Available at SSRN: https://ssrn.com/abstract=3707638 or http://dx.doi.org/10.2139/ssrn.3707638
This version of the paper has not been formally peer reviewed.

Girish Ramesh

Saarland University - Molecular Biophysics

Stadtwald
Saarbrucken, D-66123
Germany

Lukas Jarzembowksi

Saarland University - Molecular Biophysics

Yvonne Schwarz

Saarland University - Molecular Neurophysiology

Stadtwald
Saarbrucken, D-66123
Germany

Maik Konrad

Saarland University - Molecular Biophysics

Stadtwald
Saarbrucken, D-66123
Germany

Vanessa Poth

Saarland University - Molecular Biophysics

Gertrud Schwaer

Saarland University - Biophysics

Stadtwald
Saarbrucken, D-66123
Germany

Anna A. Lauer

Saarland University - Experimental Neurology

Stadtwald
Saarbrucken, D-66123
Germany

Marcus O.W. Grimm

Saarland University - Experimental Neurology

Stadtwald
Saarbrucken, D-66123
Germany

Dalia Alansary

Saarland University - Molecular Biophysics

Dieter Bruns

Saarland University - Molecular Neurophysiology

Stadtwald
Saarbrucken, D-66123
Germany

Barbara Anne Niemeyer (Contact Author)

Saarland University - Center for Integrative Physiology and Molecular Medicine (CIPMM) ( email )

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