Switching of cardiac troponin I between nuclear and cytoplasmic localization during muscle differentiation.

The nuclear accumulation of proteins may depend on the presence of short targeting sequences, which are known as nuclear localization signals (NLSs). Here, we found that NLSs are predicted in some cytosolic proteins and examined the hypothesis that these NLSs may be functional under certain conditions. As a model, human cardiac troponin I (hcTnI) was used. After expression in cultured non-muscle or undifferentiated muscle cells, hcTnI accumulated inside nuclei. Several NLSs were predicted and confirmed by site-directed mutagenesis in hcTnI. Nuclear import occurred via the classical karyopherin-α/β nuclear import pathway. However, hcTnI expressed in cultured myoblasts redistributed from the nucleus to the cytoplasm, where it was integrated into forming myofibrils after the induction of muscle differentiation. It appears that the dynamic retention of proteins inside cytoplasmic structures can lead to switching between nuclear and cytoplasmic localization.