One of the mechanisms of calcium signalling in neurons is store-operated calcium entry (SOCE), which is activated when the calcium concentration in the smooth endoplasmic reticulum (ER) decreases and its protein-calcium sensor STIM (stromal interacting molecule) relocate to the endoplasmic reticulum and plasma membrane junctions, forms clusters and induces calcium entry. In electrically non-excitable cells, STIM1 is coupled with the positive end of a tubulin microtubule through interaction with EB1 (end-binding) protein, which controls its oligomerization, SOCE and participates in ER movement. STIM2 homologue, which is specific for mature hippocampal dendritic spines, is known to interact with EB3 protein, however, not much is known about the role of this interaction in STIM2 clustering or ER trafficking in neurons.
View Article and Find Full Text PDFDendritic spine morphology is associated with the current state of the synapse and neuron, and changes during synaptic plasticity in response to stimulus. At the same time, dendritic spine alterations are reported during various neurodegenerative and neurodevelopmental disorders and other brain states. Accurate and informative analysis of spine shape has an urgent need for studying the synaptic processes and molecular pathways in normal and pathological conditions, and for testing synapto-protective strategies during preclinical studies.
View Article and Find Full Text PDFAlzheimer's disease (AD) is a neurodegenerative disorder that affects memory formation and storage processes. Dysregulated neuronal calcium (Ca) has been identified as one of the key pathogenic events in AD, and it has been suggested that pharmacological agents that stabilize Ca neuronal signaling can act as disease-modifying agents in AD. In previous studies, we demonstrated that positive allosteric regulators (PAMs) of the sarco/endoplasmic reticulum Ca ATPase (SERCA) pump might act as such Ca-stabilizing agents and exhibit neuroprotective properties.
View Article and Find Full Text PDFMany biological studies require high-resolution imaging and subsequent analysis of cell organelles and molecules. Some membrane proteins form tight clusters, and this process is directly linked to their function. In most studies, these small protein clusters have been investigated by total internal reflection fluorescence (TIRF) microscopy, which enables imaging with high spatial resolution within 100 nm of the membrane surface.
View Article and Find Full Text PDFAlzheimer's disease (AD) is the most common cause of dementia. An early feature of the AD pathology is the dysregulation of intracellular Ca signaling in neurons. In particular, increased Ca release from endoplasmic reticulum-located Ca channels, including inositol-1,4,5-trisphosphate type 1 receptors (IPR1) and ryanodine receptors type 2 (RyR2), have been extensively reported.
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