The conserved NDR kinase Orb6 controls polarized cell growth by spatial regulation of the small GTPase Cdc42.
The conserved NDR kinase regulates cell morphogenesis and polarized cell growth in different eukaryotic cells ranging from yeast to neurons. Although studies have unraveled the mechanism of regulation of NDR kinase activity, the mechanism of morphology control by NDR and the effectors that mediate NDR function are unknown. Via a chemical genetic approach, we show that the fission yeast NDR homolog, Orb6 kinase, maintains polarized cell growth at the cell tips by spatially regulating the localization of Cdc42 GTPase, a key morphology regulator. Loss of Orb6 kinase activity leads to the recruitment of Cdc42 GTPase and the Cdc42-dependent formin For3, normally found only at the cell tips, to the cell sides. Furthermore, we show that loss of Orb6 kinase activity leads to ectopic lateral localization of the Cdc42 guanine nucleotide exchange factor (GEF) Gef1, but not of the other Cdc42 GEF, Scd1. Consistent with these observations, gef1 deletion suppresses the increased cell diameter phenotype of orb6 mutants. In contrast, the microtubule cytoskeleton and the localization of the microtubule-dependent polarity markers Tea1 and Tea4 are not altered by loss of Orb6 kinase activity. Our findings indicate that the conserved NDR kinase Orb6 regulates cell polarity by spatially restricting the localization and activity of Cdc42 GTPase.
Das
Maitreyi
M
Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33101-1015, USA.
Wiley
David J
DJ
Chen
Xi
X
Shah
Kavita
K
Verde
Fulvia
F
D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D049108:Cell Enlargement; D016764:Cell Polarity; D003599:Cytoskeleton / Q000378:metabolism; D000080865:Formins; D008856:Microscopy, Fluorescence; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism / Q000502:physiology*; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000378:metabolism*
D018797:Cell Cycle Proteins; C444419:FOR3 protein, S pombe; D000080865:Formins; D029702:Schizosaccharomyces pombe Proteins; C113424:Orb6 protein, S pombe; D017346:Protein Serine-Threonine Kinases; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae