Abstract
Polarized growth is required in eukaryotic cells for processes such as cell division, morphogenesis and motility, which involve conserved and interconnected signalling pathways controlling cell cycle progression, cytoskeleton reorganization and secretory pathway functioning. While many of the factors involved in polarized growth are known, it is not yet clear how they are coordinated both spatially and temporally. Several lines of evidence point to the important role of lipid flippases in polarized growth events. Lipid flippases, which mainly belong to the P4 subfamily of P-type ATPases, are active transporters that move different lipids to the cytosolic side of biological membranes at the expense of ATP. The involvement of the Saccharomyces cerevisiae plasma membrane P4 ATPases Dnf1p and Dnf2p in polarized growth and their activation by kinase phosphorylation were established some years ago. However, these two proteins do not seem to be responsible for the phosphatidylserine internalization required for early recruitment of proteins to the plasma membrane during yeast mating and budding. In a recent publication, we demonstrated that the Golgi-localized P4 ATPase Dnf3p has a preference for PS as a substrate, can reach the plasma membrane in a cell cycle-dependent manner, and is regulated by the same kinases that activate Dnf1p and Dnf2p. This finding solves a long-lasting enigma in the field of lipid flippases and suggests that tight and heavily coordinated spatiotemporal control of lipid translocation at the plasma membrane is important for proper polarized growth.
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Acknowledgements
The author would like to thank the Novo Nordisk Foundation (NovoCrops; project number NNF19OC0056580) and the Villum Foundation (LIFER, project number 13234) for their support. Special thanks go to present and former members of the Biomembranes and Lipid flippases group, to Prof. Michael Palmgren and Prof. Anja Fuglsang for mentorship and support along the years, and to Prof. Thomas Pomorski for fruitful collaboration.
Funding
Work in the author’s group is supported by the Novo Nordisk Foundation (NovoCrops; Project Number NNF19OC0056580).
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López-Marqués, R.L. Lipid flippases in polarized growth. Curr Genet 67, 255–262 (2021). https://doi.org/10.1007/s00294-020-01145-0
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DOI: https://doi.org/10.1007/s00294-020-01145-0