Regulation of signal transduction by protein targeting: the case for CaMKII.

Protein targeting is increasingly being recognized as a mechanism to ensure speed and specificity of intracellular signal transduction in a variety of biological systems. Conceptually, this is of particular importance for second-messenger-regulated protein kinases with a broad spectrum of substrates, such as the serine/threonine protein kinases PKA, PKC, and CaMKII (cyclic-AMP-dependent protein kinase, Ca(2+)-phospholipid-dependent protein kinase, and Ca(2+)/calmodulin-dependent protein kinase II). The activating second messengers of these enzymes can be produced or released in response to a large variety of "upstream" signals, and they can, in turn, regulate a large variety of "downstream" proteins. Targeting, e.g., via anchoring proteins, can link certain incoming stimuli with specific outgoing signals by restricting the subcellular compartment at which activation and/or action of a signaling molecule can take place. Elegant research on PKA and PKC reinforced the biological importance of such mechanisms. We will focus here on CaMKII, as recent advances in the understanding of its targeting have some significant general implications for signal transduction. The interaction of CaMKII with the NMDA receptor, for instance, shows that a targeting protein can not only specify the subcellular localization of a signaling effector, but can also directly influence its regulation.     

G proteins control diverse pathways of transmembrane signaling

Hormones, neurotransmitters, and autacoids interact with specific receptors and thereby trigger a series of molecular events that ultimately produce their biological effects. These receptors, localized in the plasma membrane, carry binding sites for ligands as diverse as peptides (e.g., glucagon, neuropeptides), lipids (e.g., prostaglandins), nucleosides and nucleotides (e.g., adenosine), and amines (e.g., catecholamines, serotonin). These receptors do not interest directly with their respective downstream effector (i.e., an ion channel and/or an enzyme that synthesizes a second messenger); rather, they control one or several target systems via the activation of an intermediary guanine nucleotide-binding regulatory protein or G protein. G proteins serve as signal transducers, linking extracellularly oriented receptors to membrane-bound effectors. Traffic in these pathways is regulated by a GTP (on)-GDP (off) switch, which is regulated by the receptor. The combination of classical biochemistry and recombinant DNA technology has resulted in the discovery of many members of the G protein family. These approaches, complemented in particular by electrophysiological experiments, have also identified several effectors that are regulated by G proteins. We can safely assume that current lists of G proteins and the functions that they control are incomplete.     

BENTHIC DIATOM DISTRIBUTION IN A PENNSYLVANIA STREAM: ROLE OF pH AND NUTRIENTS1

Buffalo Creek is in a forested watershed in eastern Pennsylvania and is relatively acid in upstream reaches (pH～6), becoming alkaline downstream (pH～8). Temperature, nitrogen (NO₃-N) and phosphorus (O-PO₄) increase significantly downstream whereas N/P declines. Nutrient-diffusing substrata were deployed in triplicate at an upstream and downstream site. Six treatments included two concentrations of nitrate, two concentrations of phosphate, nitrogen + phosphate, and a control. Substrata were collected after 18 days, scraped and analyzed for accrual of chlorophyll a and algal community structure. Chlorophyll a and algal biovolume were greatest downstream across all nutrient treatments. At the community level, accrual appeared to be limited by phosphorus at upstream sites. Downstream accrual also may have been phosphorus-limited, but the results were equivocal. Benthic algae on all treatments at both sites were ～96% diatoms. Minimal overlap in species composition was observed between upstream and downstream sites. Of the 75 species of diatoms encountered in the study, 58 species did not occur at the upstream site and 10 species did not occur at the downstream site. The upstream site was depauperate in species and dominated by Eunotia exigua (Bréb. ex Kütz.) Rabh., which showed a positive response to phosphorus and accounted for over 50% of the biomass across treatments. The downstream site showed a four-fold increase in species richness. Communities at this site contained some species that appeared to be phosphorus-limited, e.g. Melosira varians Ag., and others that seemed to be nitrogen-limited, e.g. Diatoma vulgare Bory and Navicula seminulum Grun. We conclude that extreme conditions upstream (low pH, high N/P) result in a species-poor community dominated by acidophilous phosphorus-limited diatoms. Increases in downstream nutrients and pH result in a relatively rich and diverse community.