Inositol signaling activities

The binding of the sperm to a receptor on the membrane of the oocyte either activates a membrane-bound phospholipase or releases a phospholipase into the oocyte. The phospholipase hydrolyses phosphatidylinositol bisphos-phate to produce the two intracellular signals, inositol tris-phosphate (IP3) and diacylglycerol within the ovum. As in other cells, the IP3 signal increases the level of cytosolic Ca + ions and the diacylglycerol (DAG) signal activates protein kinase C. 

Phosphatidylinositol (PI), a major component of membrane lipids, is formed by displacement of CMP from CMD-dialylglycerol by n/i/o-inositol.186 It is also converted into a variety of less abundant phosphory-lated derivatives that engage in signaling activities (see Fig. 11-9). In addition, PI is a component of the glycosylphosphatidylinositol (GPI) membrane anchors for suface proteins (Fig. 8-13). Free GPI anchors, lacking bound proteins, are also present in membranes. 

Cdt is related to a eukaryotic cytosolic enzyme, phosphatidyl inositol-3,4,5, triphosphate 5-phosphatase which removes the 5-phosphate group from phosphatidyl inositol-3,4,5, triphosphate. This activity is part of an intracellular signaling cascade induced by a ligand binding to a nearby receptor. Phosphatidyl inositol-3,4,5-triphosphate 5-phosphatase possesses an Src Homology 2 (SH2) domain in addition to its Inositol Phosphatase activity (SHIP). 

Excitation of smooth muscle via alpha-1 receptors (eg, in the utems, vascular smooth muscle) is accompanied by an increase in intraceUular-free calcium, possibly by stimulation of phosphoUpase C which accelerates the breakdown of polyphosphoinositides to form the second messengers inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 releases intracellular calcium, and DAG, by activation of protein kinase C, may also contribute to signal transduction. In addition, it is also thought that alpha-1 adrenergic receptors may be coupled to another second messenger, a pertussis toxin-sensitive G-protein that mediates the translocation of extracellular calcium. 

Depletion of ATP in the cells prevents maintenance of the membrane potential, inhibits the functioning of ion pumps, and attenuates cellular signal transduction (e.g., formation of second messengers such as inositol phos phates or cyclic AMP). A marked ATP depletion ultimately impairs the activ-itv of the cell and leads to ceil death. 

Inositol trisphosphate Receptor/G-protein cascades. As discussed above, IP3 is one of the products of the hydrolysis of PIP2. To say that it acts as a second messenger means that a rise in its concentration occurs as a result of some meaningful event and that the rise causes some other significant event. In terms of information flow, the signal immediately preceding the rise in IP3 is a rise in the concentration of active PLC. This rise is due to the binding of a subset of G-proteins... 

Figure 1. Simplified schematic of receptor-mediated signal transduction in neutrophils. Binding of ligand to the receptor activates a guanine-nucleotide-binding protein (G protein), which then stimulates phospholipase C. Phosphatidylinositol 4,5-bis-phosphate is cleaved to produce diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG stimulates protein kinase C. IP3 causes the release of Ca from intracellular stores, which results in an increase in the cytosolic Ca concentration. This increase in Ca may stimulate protein kinase C, calmodulin-dependent protein kinases, and phospholipase A2. Protein phosphorylation events are thought to be important in stimulating degranulation and oxidant production. In addition, ionic fluxes occur across the plasma membrane. It is possible that phospholipase A2 and ionic channels may be governed by G protein interactions. ...

Figure 3.1 Schematic representation of a generic excitatory synapse in the brain. The presynaptic terminal releases the transmitter glutamate by fusion of transmitter vesicles with the nerve terminal membrane. Glutamate diffuses rapidly across the synaptic cleft to bind to and activate AMPA and NMDA receptors. In addition, glutamate may bind to metabotropic G-protein-coupled glutamate receptors located perisynaptically to cause initiation of intracellular signalling via the G-protein, Gq, to activate the enzyme phospholipase and hence produce inositol triphosphate (IP3) which can release Ca from intracellular calcium stores...

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