Cellular Ca2+ signals come in many flavors—from long-lasting global increases to waves to brief local plumes. Each flavor is translated into a specific cellular response by Ca2+ sensors, including calmodulin and conventional PKCs (cPKCs).
Upon Ca2+ binding, PKCα—a common cPKC—translocates to the plasma membrane, the location of most of its targets, including ion channels and transporters. The bulkiness of PKCα might suggest that its diffusion constants should be too low for rapidly following the fast and brief Ca2+ signals. Many researchers thus suspected that tiny calmodulin must be the main translator of these signals.
But the new findings reveal that PKCα is fleet footed. The authors found that PKCα's membrane translocation mimics—in both space and time—the full range of the cellular Ca2+ signals.
Just fractions of a second after a Ca2+ burst, PKCα was found at the membrane, where it lingered either for mere milliseconds or for longer stretches of several seconds. The short-lived membrane residence solely depended on cytosolic Ca2+. The more intimate interactions required PKCα's binding to the membrane lipid diacylglycerol (DAG). Since this binding is required for full activation of the kinase, the authors suspect that the shorter interactions might not necessarily lead to downstream signaling events.
Copies of PKCα that encounter Ca2+ in the center of the cell are unlikely ever to make it to the plasma membrane, as the Ca2+-PKCα complex is short lived. The authors thus suggest that PKCα activation depends solely on sub–plasma membrane Ca2+ signals. Perinuclear signals probably trigger an entirely different set of downstream events—perhaps via calmodulin, which has many cytoplasmic substrates.