Like cars, organelles obey traffic rules, moving and stopping when bid to do so by traffic control. In many cases, instead of simply switching off their motor, organelles choose to dump it altogether and pick it up again the next time they need to move. This is the case for melanosomes, which use the molecular motor myosin-V to move along actin tracks during interphase, but release it during mitosis when most membrane transport is put on hold.
The Gelfand group showed two years ago that myosin-V associates with melanosomes in Xenopus laevis melanophores and that it is phosphorylated during mitosis, which leads to its release and a marked reduction in the actin-based motility of the organelles. The same group now reports in Science that they have found the kinase responsible for this molecular switch.
Karcher and colleagues show that, as expected, myosin-V binds to melanosomes through its globular tail domain, which also contains the mitotic phosphorylation site. Combining multidimensional mass spectrometry with mutagenesis, they mapped the phosphorylation site to a single serine at position 1650.
This serine lies in a consensus phosphorylation site for calcium–calmodulin-dependent protein kinase II (CaMKII), and purified brain CaMKII indeed phosphorylates myosin-V at this site. Moreover, inhibitors of CaMKII block myosin-V phosphorylation during mitosis, preventing the release of the motor from melanosomes.
So it seems that CaMKII is responsible for the specific release of myosin-V from melanosomes during mitosis. It will be equally interesting to next find out how these organelles recruit their motor again at the end of mitosis to resume their place in traffic.
References
ORIGINAL RESEARCH PAPER
Karcher, R. L. et al. Cell cycle regulation of myosin-V by calcium–calmodulin-dependent protein kinase II. Science 293, 1317–1320 (2001)
FURTHER READING
Rogers, S. L. et al. Regulation of melanosome movement in the cell cycle by reversible association with myosin V. J. Cell Biol. 146, 1265–1276 (1999)
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Gagescu, R. Switch off your engine!. Nat Rev Mol Cell Biol 2, 642 (2001). https://doi.org/10.1038/35089551
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DOI: https://doi.org/10.1038/35089551