A novel interplay between GEFs orchestrates Cdc42 activity during cell polarity and cytokinesis
Preprint posted on 5 July 2019 https://www.biorxiv.org/content/10.1101/364786v4.full
Article now published in Journal of Cell Science at http://dx.doi.org/10.1242/jcs.236018
How do GEFs work as a team? This recent preprint by @DasLab_Pombe's group, sheds light on how fission yeast GEFs function together in order to maintain proper cell growth and division.Leeba Ann Chacko
Cell polarity is critical for maintaining cell shape, proper development, and thus survival of a cell; it also enables the execution of cellular tasks such as migration, neuronal firing, transport of nutrients across a cell, proper maintenance of cell-cell adhesions as well as the determination of the division plane of a cell. Due to the presence of conserved polarity markers, fission yeast is an ideal model organism to study the mechanism behind cell polarity.
The rod-shaped cells of fission yeast grow by extending their cell ends. During the cell cycle, the cells initially grow in a uni-directional manner from one end. Later, when the cells grow to a length of about 9.0-9.5 microns, they begin to grow from the ‘new end’ which came from the septum from the previous cell cycle. This uni-polar to bi-polar growth is known as ‘new end take-off’ (NETO). Finally, upon reaching a length of around 14 microns, the cells divide.
Cell division control protein 42 homolog (Cdc42), as the name suggests, is a conserved protein involved in regulating the cell cycle. Cdc42 also helps maintain cell polarity and its loss causes disruptions in both cell shape and division. Hercyk et al. were able to identify the intricate interplay between the Cdc42 activators, Gef1 and Scd1, in regulating Cdc42 activity during cell growth and division. This spatiotemporal modulation of Cdc42 activity is essential in maintaining cell shape, bipolar growth, and timely cell division.
1. Gef1 is required to enable cell growth to transition from monopolar to bipolar growth and this is made possible through the Gef1-mediated bipolar localization of both Scd2 and Scd1 to the poles of the cell. In the absence of Gef1, many cells show monopolar localization of both Scd2 and Scd1 and as a consequence, many of these cells grow in a monopolar fashion until cell division.
2. To understand how the Cdc42 GEFs are temporally regulated, the cell division site was used as a reference point. Hercyk et al. showed that when Gef1 localizes to the division plane, activated Cdc42 acts as an anchor for the scaffolding protein Scd2 to bind to it. The presence of Scd2 in turn recruits Scd1 to the division plane. The presence of Scd1 inhibits Gef1 at the division site post ring constriction to enable the timely separation of the daughter cells.
3. Similarly, during cell growth, Gef1 is required to activate the bipolar localization of Cdc42. In the presence of Gef1, Scd2 binds to this active Cdc42 and this, in turn, recruits Scd1 to the poles of the cell thus enabling the transition from monopolar to bipolar growth (NETO – new end take off). During cell growth, the presence of Scd1 prevents the abnormal activation of Cdc42 at the cell sides.
What I liked about this preprint:
Several players that are involved in maintaining polarity have been identified. However, the relationship between these players and the precise mechanism by which they regulate Cdc42 had not yet been elucidated. Hercyk et al. showed that the two Cdc42 GEFs, Gef1 and Scd1, spatiotemporally activate each other in order to regulate Cdc42 activity at the division site. This GEF-mediated regulation of Cdc42 is also essential to assist cell polarity during interphase after cell division has occurred.
- Hercyk, B. S., Rich-Robinson, J. T., Mitoubsi, A. S., Harrell, M. A., & Das, M. E. (2019). A novel interplay between GEFs orchestrates Cdc42 activity during cell polarity and cytokinesis. bioRxiv, 9(2), 364786. http://doi.org/10.1101/364786
- Mitchison, J. M., & Nurse, P. (1985). Growth in cell length in the fission yeast Schizosaccharomyces pombe. Journal of Cell Science, 75(1), 357–376.
- Wei, B., Hercyk, B. S., Mattson, N., Mohammadi, A., Rich, J., DeBruyne, E., et al. (2016). Unique spatiotemporal activation pattern of Cdc42 by Gef1 and Scd1 promotes different events during cytokinesis. Molecular Biology of the Cell, 27(8), 1235–1245. http://doi.org/10.1091/mbc.E15-10-0700
- Rincón, S. A., Estravís, M., & Pérez, P. (2014). Cdc42 regulates polarized growth and cell integrity in fission yeast. Biochemical Society Transactions, 42(1), 201–205. http://doi.org/10.1042/BST20130155
Posted on: 2 August 2019 , updated on: 18 June 2021Read preprint
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