Abstract
Protein transport toward the nucleus is important for translating molecular signals into gene expression changes. Interestingly, the unconventional motor protein myosin VI regulates RNA polymerase II-dependent gene transcription. Whether actin-filament-dependent myosins are actively transported to nuclear compartments remains unknown. Here, we report that neurons also contain myosin VI inside their nucleus. Notably, nuclear appearance of this actin-dependent motor depends on functional cytoplasmic dynein, a minus end-directed microtubule motor. We find that the trafficking factor muskelin assists in the formation of dynein-myosin VI interactions and further localizes to nuclear foci, enriched in the myosin. Impairment of dynein, but not myosin VI function, reduces nuclear muskelin levels. In turn, muskelin represents a critical determinant in regulating myosin VI nuclear targeting. Our data reveal that minus end-directed microtubule transport determines myosin VI subcellular localization. They suggest a pathway of cytoplasm-to-nucleus trafficking that requires muskelin and is based on dynein-myosin cross talk.