Interaction between importin 13 and myopodin suggests a nuclear import pathway for myopodin.

Importin 13 is a member of the importin beta superfamily of nuclear transport proteins and is expressed in multiple tissues at high levels both in humans and rodents, including fetal lung, brain, and heart. In order to elucidate potential functions of imp13 in the heart, we have used rat imp13 as bait to screen a human heart cDNA library and identified an interaction with the C-terminal peptide of myopodin (a.a. 360-698), an actin-bundling protein, associated with tumor-suppressor activity that localizes to both the cytoplasm and the nucleus. We have used GST-pull down assays and co-immunoprecipitation experiments to demonstrate an interaction between imp13 and full-length myopodin and observed that RanGTP dissociates the myopodin-imp13 complex. In studies of cultured cells, we show that both imp13 siRNA and a C-terminal fragment of imp13 protein prevent nuclear localization of myopodin. We, therefore, conclude that imp13 functions in myopodin import and we suggest that the regulation of these events is critical for normal and abnormal cellular differentiation.