Role of the nuclear envelope in calcium signalling.

The endoplasmic reticulum (ER) is the major Ca(2+) store inside the cell. Its organisation in specialised subdomains allows the local delivery of Ca(2+) to specific cell areas on stimulation. The nuclear envelope (NE), which is continuous with the ER, has a double role: it insulates the nucleoplasm from the cytoplasm and it stores Ca(2+) around the nucleus.

Differential redistribution of Ca2+-handling proteins during polarisation of MDCK cells: Effects on Ca2+ signalling.

The spatial organisation of the Ca(2+) signal in microdomains enables the regulation of various processes in specific regions of the cell and is essential for the versatility of cell responses to various stimuli. Ca(2+) signals can be independently regulated in the cytoplasm and in the nucleoplasm. Increases in the concentration of Ca(2+) in the nucleus can have specific effects different from those due to increases of Ca(2+) in the cytoplasm.

Dynamics of the Ins(1,4,5)P3 receptor during polarization of MDCK cells.

Background Information: The uneven distribution of the Ins(1,4,5)P3R [Ins(1,4,5)P3 receptor] within the ER (endoplasmic reticulum) membrane generates spatially complex Ca2+ signals. The ER is a dynamic network, which allows the rapid diffusion of membrane proteins from one part of the cell to another. However, little is known about the localization and the dynamics of the Ins(1,4,5)P3R in the ER of living cells.

Subcellular distribution of the inositol 1,4,5-trisphosphate receptors: functional relevance and molecular determinants.

The inositol 1,4,5-trisphosphate receptor (IP3R) is an intracellular Ca2+ channel that is for the largest part expressed in the endoplasmic reticulum. Its precise subcellular localization is an important factor for the correct initiation and propagation of Ca2+ signals. The relative position of the IP3Rs, and thus of the IP3-sensitive Ca2+ stores, to mitochondria, nucleus or plasma membrane determines in many cases the physiological consequences of IP3-induced Ca2+ release.

Regulation of the cerebellar inositol 1,4,5-trisphosphate receptor by univalent cations.

In the present study we investigated the effects of K and other univalent cations on [3H]InsP3 [[3H]Ins(1,4,5)P3] binding to sheep cerebellar microsomes. In equilibrium binding experiments performed over 4 s at pH 7.1 and 20 degrees C, the addition of K to the binding medium decreased the affinity and increased the total number of binding sites for InsP3 in a dose-dependent manner.

The type 3 inositol 1,4,5-trisphosphate receptor is concentrated at the tight junction level in polarized MDCK cells.

The subcellular localization of inositol 1,4,5-trisphosphate (InsP3)-induced Ca2+ signals is important for the activation of many physiological functions. In epithelial cells the spatial distribution of InsP3 receptor is restricted to specific areas, but little is known about the relationship between the receptor's distribution and cell polarity. To investigate this relationship, the best known polarized cell model, MDCK, was examined.

D-myo-inositol-1,4,5-trisphosphate and adenophostin mimics: importance of the spatial orientation of a phosphate group on the biological activity.

Three different routes for the synthesis of heterocyclic analogues of the second messenger D-myo-inositol-1,4,5-trisphosphate (InsP(3)) and the natural adenophostins, starting from allyl D-xyloside are described. The two diastereoisomers at C-2 of new compounds, which we named xylophostins, were obtained. The preliminary biological studies shows that the presence of the adenine residue has a beneficial effect on the affinity for the receptor.