Alternatively spliced STIM2.3 is an evolutionarily late store-operated Ca2+ entry regulator expressed in brain

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Calcium (Ca2+) homeostasis is crucial for cellular functions.
• Store-Operated Calcium Entry (SOCE) regulates Ca2+ levels.
• STIM proteins (STIM1 and STIM2) are key regulators of SOCE.

Purpose of the Study:

• To characterize a novel, short STIM2 variant (STIM2.3) found in humans and old-world monkeys.
• To investigate the functional impact of STIM2.3 on SOCE, NFAT activation, and neuronal morphology.
• To explore the potential role of STIM2.3 in brain evolution and complexity.

Main Methods:

• Structure-function analysis of STIM2 variants.
• Measurement of Ca2+ entry.
• Analysis of NFAT activation.
• Neuronal imaging to assess dendritic spine morphology.

Main Results:

• STIM2.3, despite lacking the polybasic domain, effectively increased SOCE.
• STIM2.3 demonstrated altered interactions with AMPK.
• Neuronal expression of STIM2.3 led to enlarged dendritic spine heads compared to STIM2.2.
• STIM2.3 showed reduced interaction with activated AMPK.

Conclusions:

• STIM2.3 possesses unique functional properties, including enhanced SOCE and modulation of dendritic spine morphology.
• The specific expression and function of STIM2.3 in the brain suggest a role in neuronal plasticity and potentially in the evolution of brain complexity.
• Regulated splicing of STIM2.3 in the brain may offer a rapid mechanism to influence gene expression, neuronal structure, and excitability.