An S-glutathiomimetic Provides Structural Insights into Stromal Interaction Molecule-1 Regulation.

Stromal interaction molecule 1 (STIM1) is an endo/sarcoplasmic reticulum (ER/SR) calcium (Ca) sensing protein that regulates store-operated calcium entry (SOCE). In SOCE, STIM1 activates Orai1-composed Ca channels in the plasma membrane (PM) after ER stored Ca depletion. S-Glutathionylation of STIM1 at Cys56 evokes constitutive SOCE in DT40 cells; however, the structural and biophysical mechanisms underlying the regulation of STIM1 by this modification are poorly defined.

Scholarly Impact of Academic Ophthalmologists and Vision Scientists in Canada.

Objective: To outline the current impact of Canadian ophthalmology and vision science research as measured by novel research metrics.

Design: Cross-sectional survey.

Participants: All Canadian ophthalmologists (n = 687) and vision scientists (n = 119) with an online bibliometric profile and academic appointment at a major ophthalmology training centre were included.

Lactate Elicits ER-Mitochondrial Mg Dynamics to Integrate Cellular Metabolism.

Mg is the most abundant divalent cation in metazoans and an essential cofactor for ATP, nucleic acids, and countless metabolic enzymes. To understand how the spatio-temporal dynamics of intracellular Mg (Mg) are integrated into cellular signaling, we implemented a comprehensive screen to discover regulators of Mg dynamics. Lactate emerged as an activator of rapid release of Mg from endoplasmic reticulum (ER) stores, which facilitates mitochondrial Mg (Mg) uptake in multiple cell types.

Synergistic stabilization by nitrosoglutathione-induced thiol modifications in the stromal interaction molecule-2 luminal domain suppresses basal and store operated calcium entry.

Stromal interaction molecule-1 and -2 (STIM1/2) are endoplasmic reticulum (ER) membrane-inserted calcium (Ca) sensing proteins that, together with Orai1-composed Ca channels on the plasma membrane (PM), regulate intracellular Ca levels. Recent evidence suggests that S-nitrosylation of the luminal STIM1 Cys residues inhibits store operated Ca entry (SOCE). However, the effects of thiol modifications on STIM2 during nitrosative stress and their role in regulating basal Ca levels remain unknown.

Structural Mechanisms of Store-Operated and Mitochondrial Calcium Regulation: Initiation Points for Drug Discovery.

Calcium (Ca) is a universal signaling ion that is essential for the life and death processes of all eukaryotes. In humans, numerous cell stimulation pathways lead to the mobilization of sarco/endoplasmic reticulum (S/ER) stored Ca, resulting in the propagation of Ca signals through the activation of processes, such as store-operated Ca entry (SOCE). SOCE provides a sustained Ca entry into the cytosol; moreover, the uptake of SOCE-mediated Ca by mitochondria can shape cytosolic Ca signals, function as a feedback signal for the SOCE molecular machinery, and drive numerous mitochondrial processes, including adenosine triphosphate (ATP) production and distinct cell death pathways.

Structural elements of stromal interaction molecule function.

Stromal interaction molecule (STIM)-1 and -2 are multi-domain, single-pass transmembrane proteins involved in sensing changes in compartmentalized calcium (Ca) levels and transducing this cellular signal to Orai1 channel proteins. Our understanding of the molecular mechanisms underlying STIM signaling has been dramatically improved through available X-ray crystal and solution NMR structures. This high-resolution structural data has revealed that intricate intramolecular and intermolecular protein-protein interactions are involved in converting STIMs from the quiescent to activation-competent states.