@article {79802, title = {SEPT7 regulates Ca entry through Orai channels in human neural progenitor cells and neurons.}, journal = {Cell Calcium}, volume = {90}, year = {2020}, month = {2020 Jul 09}, pages = {102252}, abstract = {

Human neural progenitor cells (hNPCs) are self-renewing cells of neural lineage that can be differentiated into neurons of different subtypes. Here we show that SEPT7, a member of the family of filament-forming GTPases called septins, prevents constitutive Ca entry through the store-operated Ca entry channel, Orai in hNPCs and in differentiated neurons and is thus required for neuronal calcium homeostasis. Previous work in Drosophila neurons has shown that loss of one copy of the evolutionarily-conserved dSEPT7 gene leads to elevated Ca entry via Orai, in the absence of ER-Ca store depletion. We have identified an N-terminal polybasic region of SEPT7, known to interact with membrane-localized phospholipids, as essential for spontaneous calcium entry through Orai in hNPCs, whereas the GTPase domain of dSEPT7 is dispensable for this purpose. Re-organisation of Orai1 and the ER-Ca sensor STIM1 observed near the plasma membrane in SEPT7 KD hNPCs, supports the idea that Septin7 containing heteromers prevent Ca entry through a fraction of STIM-Orai complexes. Possible mechanisms by which SEPT7 reduction leads to opening of Orai channels in the absence of store-depletion are discussed.

}, issn = {1532-1991}, doi = {10.1016/j.ceca.2020.102252}, author = {Deb, Bipan K and Chakraborty, Pragnya and Gopurappilly, Renjitha and Hasan, Gaiti} } @article {7589, title = {Mutant IP3 receptors attenuate store-operated Ca2+ entry by destabilizing STIM-Orai interactions in Drosophila neurons.}, journal = {J Cell Sci}, year = {2016}, month = {2016 Sep 2}, abstract = {

Store-operated Ca(2+) entry (SOCE) occurs when loss of Ca(2+) from the endoplasmic reticulum (ER) stimulates the Ca(2+) sensor, STIM, to cluster and activate the plasma membrane (PM) Ca(2+) channel, Orai. Inositol 1,4,5-trisphosphate receptors (IP3R) are assumed to regulate SOCE solely by mediating ER Ca(2+) release. We show that in Drosophila neurons, mutant IP3R attenuate SOCE evoked by depleting Ca(2+) stores with thapsigargin. In normal neurons, store depletion caused STIM and IP3R to accumulate near the PM, association of STIM with Orai, clustering of STIM and Orai at ER-PM junctions, and activation of SOCE. These responses were attenuated in neurons with mutant IP3R and rescued by over-expression of STIM with Orai. We conclude that after depletion of Ca(2+) stores in Drosophila, translocation of IP3R to ER-PM junctions facilitates the coupling of STIM to Orai that leads to activation of SOCE.

}, issn = {1477-9137}, doi = {10.1242/jcs.191585}, author = {Chakraborty, Sumita and Deb, Bipan K and Chorna, Tetyana and Konieczny, Vera and Taylor, Colin W and Hasan, Gaiti} } @article {11585, title = {Regulation of Store-Operated Ca(2+) Entry by Septins.}, journal = {Front Cell Dev Biol}, volume = {4}, year = {2016}, month = {2016}, pages = {142}, abstract = {

The mechanism of store-operated Ca(2+) entry (SOCE) brings extracellular Ca(2+) into cells after depletion of intracellular Ca(2+) stores. Regulation of Ca(2+) homeostasis by SOCE helps control various intracellular signaling functions in both non-excitable and excitable cells. Whereas essential components of the SOCE pathway are well characterized, molecular mechanisms underlying regulation of this pathway need investigation. A class of proteins recently demonstrated as regulating SOCE is septins. These are filament-forming GTPases that assemble into higher order structures. One of their most studied cellular functions is as a molecular scaffold that creates diffusion barriers in membranes for a variety of cellular processes. Septins regulate SOCE in mammalian non-excitable cells and in Drosophila neurons. However, the molecular mechanism of SOCE-regulation by septins and the contribution of different subgroups of septins to SOCE-regulation remain to be understood. The regulation of SOCE is relevant in multiple cellular contexts as well as in diseases, such as the Severe Combined Immunodeficiency (SCID) syndrome and neurodegenerative syndromes like Alzheimer{\textquoteright}s, Spino-Cerebellar Ataxias and Parkinson{\textquoteright}s. Moreover, Drosophila neurons, where loss of SOCE leads to flight deficits, are a possible cellular template for understanding the molecular basis of neuronal deficits associated with loss of either the Inositol-1,4,5-trisphosphate receptor (IP3R1), a key activator of neuronal SOCE or the Endoplasmic reticulum resident Ca(2+) sensor STIM1 (Stromal Interaction Molecule) in mouse. This perspective summarizes our current understanding of septins as regulators of SOCE and discusses the implications for mammalian neuronal function.

}, doi = {10.3389/fcell.2016.00142}, author = {Deb, Bipan K and Hasan, Gaiti} }