page 27, Liu et al. find that the nuclear localization of a transcription factor may be the key to this switch.
Liu et al. applied electrical pulses to isolated adult murine muscle fibers, thus simulating fast-twitch and slow-twitch muscle stimulation in vitro. They then looked at the localization of the transcription factor NFATc, which has been implicated in muscle- and T-cell transcriptional regulation.
NFATc is cytoplasmic in unstimulated fast-twitch muscle fibers, but translocates to distinct nuclear foci when the fibers are exposed to kinase inhibitors or trains of electrical pulses at 10 Hz, simulating slow-twitch stimulation. Two conditions do not cause NFATc nuclear-translocation: simulated fast-twitch stimulation, and continuous 1 Hz stimulation, which provides the same number of electrical jolts per minute as the 10 Hz pulses without mimicking any natural stimulation pattern.
The nuclear NFATc localizes to distinct intranuclear foci. Liu et al. report that the foci are similar in size and shape to the Cajal bodies that are believed to be involved in splicing in certain cells, but the two structures may not be the same. The authors are now trying to identify additional components of the NFATc-containing foci, and hope to use their in vitro system to determine whether NFATc translocation alone is sufficient to initiate the conversion of fast-twitch muscle fibers into slow-twitch fibers. ▪