Loss of endoplasmic reticular (ER) Ca activates store-operated Ca entry (SOCE) by causing the ER localized Ca sensor STIM to unfurl domains that activate Orai channels in the plasma membrane at membrane contact sites (MCS). Here, we demonstrate a novel mechanism by which the inositol 1,4,5 trisphosphate receptor (IPR), an ER-localized IP-gated Ca channel, regulates neuronal SOCE. In human neurons, SOCE evoked by pharmacological depletion of ER-Ca is attenuated by loss of IPRs, and restored by expression of IPRs even when they cannot release Ca, but only if the IPRs can bind IP.
View Article and Find Full Text PDFCalcium imaging in an ex-vivo setup is used to understand the calcium status of isolated cells or tissue. In this chapter we explain the use of the ratiometric chemical indicator Fura-2 which can be loaded into isolated cells in the form of lipophilic acetomethyl (AM) esters. Fura-2 is a combination of calcium chelator and fluorophore, and can be used with dual wavelength excitation (340/380 nm) for quantitative calcium concentrations.
View Article and Find Full Text PDFOrganisms need to coordinate growth with development, particularly in the context of nutrient availability. Thus, multiple ways have evolved to survive extrinsic nutrient deprivation during development. In , growth occurs during larval development.
View Article and Find Full Text PDFCa signaling plays a significant role in the development of the vertebrate nervous system where it regulates neurite growth as well as synapse and neurotransmitter specification. Elucidating the role of Ca signaling in mammalian neuronal development has been largely restricted to either small animal models or primary cultures. Here we derived human neural precursor cells (NPCs) from human embryonic stem cells to understand the functional significance of a less understood arm of calcium signaling, Store-operated Ca entry or SOCE, in neuronal development.
View Article and Find Full Text PDFOrai channels are required for store-operated Ca(2+) entry (SOCE) in multiple cell types. Septins are a class of GTP-binding proteins that function as diffusion barriers in cells. Here we show that Septin 7 acts as a 'molecular brake' on activation of Orai channels in Drosophila neurons.
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