Biosynthetic infochemical communication.

There is an ever-increasing demand for data to be embedded in our environment at ever-decreasing temporal and spatial scales. Whilst current communication and storage technologies generally exploit the electromagnetic properties of media, chemistry offers us a new alternative for nanoscale signaling using molecules as messengers with high information content. Biological systems effectively overcome the challenges of chemical communication using highly specific biosynthetic pathways for signal generation together with specialized protein receptors and nervous systems. Here we consider a new approach for information transmission based upon nature's quintessential example of infochemical communication, the moth pheromone system. To approach the sensitivity, specificity and versatility of infochemical communication seen in nature, we describe an array of biologically-inspired technologies for the production, transmission, detection, and processing of molecular signals. We show how it is possible to implement each step of the moth pheromone pathway for biosynthesis, transmission, receptor protein binding/transduction, and antennal lobe processing of monomolecular and multimolecular signals. For each implemented step, we discuss the value, current limitations, and challenges for the future development and integration of infochemical communication technologies. Together, these building blocks provide a starting point for future technologies that can utilize programmable emission and detection of multimolecular information for a new and robust means of communicating chemical information.

Defining protein kinase/phosphatase isoenzymic regulation of mGlu5 receptor-stimulated phospholipase C and Ca²âº responses in astrocytes.

BACKGROUND AND PURPOSE: Cyclical phosphorylation and dephosphorylation of a key residue within the C-terminal domain of the activated type 5 metabotropic glutamate (mGlu5) receptor is believed to cause the synchronous, oscillatory changes in inositol 1,4,5-trisphosphate and Ca²âº levels observed in a variety of cell types. Here, we have attempted to better define the kinase and phosphatase enzymes involved in this modulation. EXPERIMENTAL APPROACH: Ca²âº and [³H]inositol phosphate ([³H]IP(x) ) measurements in astrocyte preparations have been used to evaluate the effects of pharmacological inhibition of protein kinase C (PKC) and protein phosphatase activities and small interfering RNA-mediated specific PKC isoenzymic knock-down on mGlu5 receptor signalling. KEY RESULTS: Ca²âº oscillation frequency or [³H]IP(x) accumulation in astrocytes stimulated by mGlu5 receptors, was concentration-dependently decreased by protein phosphatase-1/2A inhibition or by PKC activation. PKC inhibition also increased [³H]IP(x) accumulation two- to threefold and changed the Ca²âº response into a peak-plateau response. However, selective inhibition of conventional PKC isoenzymes or preventing changes in [Ca²âº](i) concentration by BAPTA-AM loading was without effect on mGlu5 receptor-stimulated [³H]IP(x) accumulation. Selective knock-down of PKCδ was without effect on glutamate-stimulated Ca²âº responses; however, selective PKCε knock-down in astrocytes changed Ca²âº responses from oscillatory into peak-plateau type. CONCLUSION AND IMPLICATIONS: These data confirm the acute regulation of mGlu5 receptor signalling by protein kinases and protein phosphatases and provide novel data pinpointing the isoenzymic dependence of this regulation in the native mGlu5 receptor-expressing rat cortical astrocyte. These data also highlight a potential alternative mechanism by which mGlu5 receptor signalling might be therapeutically manipulated.