Phosphorylation-dependent inhibition of Cdc42 GEF Gef1 by 14-3-3 protein Rad24 spatially regulates Cdc42 GTPase activity and oscillatory dynamics during cell morphogenesis
Das, Maitreyi E.
Wiley, David J.
Yates, John R.
MetadataShow full item record
Active Cdc42 GTPase, a key regulator of cell polarity, displays oscillatory dynamics that are anticorrelated at the two cell tips in fission yeast. Anticorrelation suggests competition for active Cdc42 or for its effectors. Here we show how 14-3-3 protein Rad24 associates with Cdc42 guanine exchange factor (GEF) Gef1, limiting Gef1 availability to promote Cdc42 activation. Phosphorylation of Gef1 by conserved NDR kinase Orb6 promotes Gef1 binding to Rad24. Loss of Rad24–Gef1 interaction increases Gef1 protein localization and Cdc42 activation at the cell tips and reduces the anticorrelation of active Cdc42 oscillations. Increased Cdc42 activation promotes precocious bipolar growth activation, bypassing the normal requirement for an intact microtubule cytoskeleton and for microtubule-dependent polarity landmark Tea4-PP1. Further, increased Cdc42 activation by Gef1 widens cell diameter and alters tip curvature, countering the effects of Cdc42 GTPase-activating protein Rga4. The respective levels of Gef1 and Rga4 proteins at the membrane define dynamically the growing area at each cell tip. Our findings show how the 14-3-3 protein Rad24 modulates the availability of Cdc42 GEF Gef1, a homologue of mammalian Cdc42 GEF DNMBP/TUBA, to spatially control Cdc42 GTPase activity and promote cell polarization and cell shape emergence.
© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Molecular Biology of the Cell 26 (2015): 3520-3534, doi:10.1091/mbc.E15-02-0095.
Suggested CitationArticle: Das, Maitreyi E., Nunez, Illyce, Rodriguez, Marbelys, Wiley, David J., Rodriguez, Juan, Sarkeshik, Ali, Yates, John R., Buchwald, Peter, Verde, Fulvia, "Phosphorylation-dependent inhibition of Cdc42 GEF Gef1 by 14-3-3 protein Rad24 spatially regulates Cdc42 GTPase activity and oscillatory dynamics during cell morphogenesis", Molecular Biology of the Cell 26 (2015): 3520-3534, DOI:10.1091/mbc.E15-02-0095, https://hdl.handle.net/1912/7687
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 3.0 Unported
Showing items related by title, author, creator and subject.
Endonuclease-containing Penelope retrotransposons in the bdelloid rotifer Adineta vaga exhibit unusual structural features and play a role in expansion of host gene families Arkhipova, Irina R.; Yushenova, Irina A.; Rodriguez, Fernando (BioMed Central, 2013-08-27)Penelope-like elements (PLEs) are an enigmatic group of retroelements sharing a common ancestor with telomerase reverse transcriptases. In our previous studies, we identified endonuclease-deficient PLEs that are associated ...
LTR-retrotransposons from Bdelloid rotifers capture additional ORFs shared between highly diverse retroelement types Rodriguez, Fernando; Kenefick, Aubrey W.; Arkhipova, Irina R. (MDPI AG, 2017-04-11)Rotifers of the class Bdelloidea, microscopic freshwater invertebrates, possess a highlydiversified repertoire of transposon families, which, however, occupy less than 4% of genomic DNA in the sequenced representative ...
The diversity of sulfide oxidation and sulfate reduction genes expressed by the bacterial communities of the Cariaco Basin, Venezuela Rodriguez-Mora, Maria J.; Edgcomb, Virginia P.; Taylor, Craig D.; Scranton, Mary I.; Taylor, Gordon T.; Chistoserdov, Andrei Y. (Bentham Open, 2016-08-31)Qualitative expression of dissimilative sulfite reductase (dsrA), a key gene in sulfate reduction, and sulfide:quinone oxidoreductase (sqr), a key gene in sulfide oxidation was investigated. Neither of the two could be ...