Conformational coupling with the inositol 1,4,5-trisphosphate (IP3) receptor has been suggested as a possible mechanism of activation of TRPC3 channels and a region in the C terminus of TRPC3 has been shown to interact with the IP3 receptor as well as calmodulin (calmodulin/IP3 receptor-binding (CIRB) region). Here we show that internal deletion of 20 amino acids corresponding to the highly con...

In saponin-permeabilized mouse lacrimal acinar cells, glycerophosphoryl-myo-inositol 4,5-bisphosphate (GPIP2) activated the release of sequestered Ca2+ to the same extent as inositol 1,4,5-trisphosphate ((1,4,5)IP3) but with a potency about 1/10 that of (1,4,5)IP3. In lacrimal gland homogenates, [3H]GPIP2 was metabolized to two compounds which upon anion exchange high performance liquid chromat...

Nuclear calcium appears to have an important role in the regulation of gene expression in many cells, but the mechanisms involved in controlling nuclear Ca2+ signaling are controversial and still poorly understood. We have described the presence of inositol 1,4,5 trisphosphate (IP3) receptors in the nuclei of skeletal muscle cells. Now, we have characterized the properties of the IP3 receptors ...

Rabphilin-3A is a neuronal C2 domain tandem containing protein involved in vesicle trafficking. Both its C2 domains (C2A and C2B) are able to bind phosphatidylinositol 4,5-bisphosphate, a key player in the neurotransmitter release process. The rabphilin-3A C2A domain has previously been shown to bind inositol-1,4,5-trisphosphate (IP3; phosphatidylinositol 4,5-bisphosphate headgroup) in a Ca2+-d...

Inositol 1,4,5-trisphosphate (IP3) stimulates Ca2+ release from the endoplasmic reticulum (ER), and the response is potentiated by 3',5'-cyclic AMP (cAMP). We investigated this interaction in HEK293 cells using carbachol and parathyroid hormone (PTH) to stimulate formation of IP3 and cAMP, respectively. PTH alone had no effect on the cytosolic Ca2+ concentration, but it potentiated the Ca2+ sig...

Rapid eye movement (REM) sleep onset is triggered by disinhibition of cholinergic neurons in the pons. During REM sleep, the brain exhibits prominent activity in the 5-8 Hz (theta) frequency range. How REM sleep onset and theta waves are regulated is poorly understood. Astrocytes, a non-neuronal cell type in the brain, respond to cholinergic signals by elevating their intracellular Ca2+ concent...

Inositol 1,4,5-trisphosphate receptor (IP3R) is a highly controlled calcium (Ca2+) channel gated by inositol 1,4,5-trisphosphate (IP3). Multiple regulators modulate IP3-triggered pore opening by binding to discrete allosteric sites within IP3R. Accordingly we have postulated that these regulators structurally control ligand gating behavior; however, no structural evidence has been available. He...

This work deals with two paradigms of cellular signaling: a change in the intracellular Ca2+ concentration represents often one of the first steps in the transduction of incoming stimuli; the ability to properly respond to external injuries and repair damaged DNA is an essential component for life. The approaches used to investigate Ca2+ signaling and DNA repair bear common points. Mathematical...

BACKGROUND The inositol 1,4,5-trisphosphate (IP3) receptor is an intracellular calcium channel that couples cell membrane receptors, via the second messenger IP3, to calcium signal transduction pathways within many types of cells. IP3 receptor function has been implicated in development, but the physiological processes affected by its function have yet to be elucidated. In order to identify the...