Intranuclear extensions of the ER have been described previously, but the Yale group is the first to show that the compartment both contains and can release calcium. Localized photorelease of inositol 1,4,5-trisphosphate (InsP3) in the nucleus resulted in a gradient of calcium that spread from the site of photorelease across the nucleus. The effects of nuclear calcium release were distinct from those of cytosolic calcium release: nuclear calcium caused translocation of a labeled protein kinase C (PKC) to the nuclear envelope, whereas cytosolic calcium triggered PKC translocation to the plasma membrane.
Several growth factor receptors are known to translocate to and signal in the nucleus. And several transcription factors—targets of signal transduction pathways—rely on calcium as one of their stimulatory inputs. As yet there is no obvious candidate pathway that combines both of these characteristics. But, if such a pathway is identified, two important factors—the site of calcium release and the proximity of target genes to this site—may help control the strength of the pathway's output. ▪