Essential control of an endothelial cell ISOC by the spectrin membrane skeleton

Abstract

Mechanism(s) underlying activation of store-operated Ca2+ entry currents, I SOC, remain incompletely understood. F-actin configuration is an important determinant of channel function, although the nature of interaction between the cytoskeleton and I SOC channels is unknown. We examined whether the spectrin membrane skeleton couples Ca2+ store depletion to Ca2+ entry. Thapsigargin activated an endothelial cell I SOC (−45 pA at −80 mV) that reversed at +40 mV, was inwardly rectifying when Ca2+ was the charge carrier, and was inhibited by La3+ (50 μM). Disruption of the spectrin–protein 4.1 interaction at residues A207-V445 of βSpIIΣ1 decreased the thapsigargin-induced global cytosolic Ca2+ response by 50% and selectively abolished the endothelial cell I SOC, without altering activation of a nonselective current through cyclic nucleotide–gated channels. In contrast, disruption of the spectrin–actin interaction at residues A47-K186 of βSpIIΣ1 did not decrease the thapsigargin-induced global cytosolic Ca2+ response or inhibit I SOC. Results indicate that the spectrin–protein 4.1 interaction selectively controls I SOC, indicating that physical coupling between calcium release and calcium entry is reliant upon the spectrin membrane skeleton.

Erythropoiesis from acetyl LDL incorporating endothelial cells at the preliver stage

“…[30][31][32][33] The first DiI ϩ illumination was observed as early as 30 minutes after inoculation. One hour later, the whole vascular tree in the YS and the embryo proper was labeled.…”

Role of EETs in regulation of endothelial permeability in rat lung

“…The link between store depletion and capacitative Ca 2ϩ entry has been thought to depend on either soluble mediators or physical coupling between the endoplasmic reticulum and plasma membrane Ca 2ϩ channel(s). Although the notion that physical coupling mechanisms are involved in EC has gained support (26,47), a link involving soluble mediators has not been ruled out. Among the candidates proposed for the latter are arachidonic acid (AA) metabolites generated via cytochrome P-450 epoxygenases (epoxyeicosatrienoic acids or EETs).…”

Stimulation of Gαq-coupled M1 muscarinic receptor causes reversible spectrin redistribution mediated by PLC, PKC and ROCK

“…One possibility is its close relation to plasma membrane-ER complexes-based signaling. First, spectrin controls storeoperated Ca 2+ entry through membrane protein 4.1 (Wu et al, 2001), and links the plasma membrane microdomain to the ER microdomain in a cell-specific manner (Lencesova et al, 2004). The cytoskeletal components link the B 2 bradykinin receptor, but not M1 mAChR, to Ins(1,4,5)P 3 R, thus, only the B 2 bradykinin receptor can activate the Ins(1,4,5)P 3 R and transient receptor potential channel 1 (TRPC1) in sympathetic neurons, whereas both G␣ q/11 -coupled receptors are able to activate Ins(1,4,5)P 3 R and TRPC1 in M1-CHO cells (Delmas et al, 2002).…”