Growth-Dependent Activation of Protein Kinases Suggests a Mechanism for Measuring Cell Growth

Jasani, Akshi; Huynh, Tiffany G.; Kellogg, Douglas R.

doi:10.1534/genetics.120.303200

Cited by 12 publications

(5 citation statements)

References 72 publications

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“…Although such regulation in M phase is known ( Leitao and Kellogg, 2017 ; Garmendia-Torres et al, 2018 ), our data suggest a sequential mechanism to match size to growth rate, with a nutrient-independent sizer followed by a nutrient-dependent timer. To detect the peak in bud growth generated by the sizer, cells may use Gin4-related kinases ( Jasani et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Determining growth rates from bright-field images of budding cells through identifying overlaps

Pietsch

Muñoz

Adjavon

et al. 2023

eLife

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Much of biochemical regulation ultimately controls growth rate, particularly in microbes. Although time-lapse microscopy visualises cells, determining their growth rates is challenging, particularly for those that divide asymmetrically, like Saccharomyces cerevisiae, because cells often overlap in images. Here we present the Birth Annotator for Budding Yeast (BABY), an algorithm to determine single-cell growth rates from label-free images. Using a convolutional neural network, BABY resolves overlaps through separating cells by size and assigns buds to mothers by identifying bud necks. BABY uses machine learning to track cells and determine lineages and estimates growth rates as the rates of change of volumes. Using BABY and a microfluidic device, we show that bud growth is likely first sizer- then timer-controlled, that the nuclear concentration of Sfp1, a regulator of ribosome biogenesis, varies before the growth rate does, and that growth rate can be used for real-time control. By estimating single-cell growth rates and so fitness, BABY should generate much biological insight.

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Section: Resultsmentioning

confidence: 99%

Determining growth rates from bright-field images of budding cells through identifying overlaps

Pietsch

Muñoz

Adjavon

et al. 2023

eLife

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“…A previous study revealed that a pantothenate transporter gene disruption mutant could not form spores [ 33 ]. In some fungi, the serine/threonine-protein kinase Gin4 was important for the septin organization and cell cycle [ 34 , 35 , 36 ]. The inactivation of Gin4 led to a prolonged mitotic delay [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…In some fungi, the serine/threonine-protein kinase Gin4 was important for the septin organization and cell cycle [ 34 , 35 , 36 ]. The inactivation of Gin4 led to a prolonged mitotic delay [ 36 ]. In the RNA-seq data, the gene for the serine/threonine-protein kinase Gin4 (MAC_00865) was upregulated, which may accelerate the process of cell division, suggesting the possibility that MaOpy2 may regulate the expression of Gin4 to shift the conidiation pattern, thus promoting the conidiation—but this needs to be further explored.…”

Section: Discussionmentioning

confidence: 99%

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MaOpy2, a Transmembrane Protein, Is Involved in Stress Tolerances and Pathogenicity and Negatively Regulates Conidial Yield by Shifting the Conidiation Pattern in Metarhizium acridum

Wen

Yang

Xia

et al. 2022

JoF

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Opy2 is an important membrane-anchored protein upstream of the HOG-MAPK signaling pathway and plays important roles in both the HOG-MAPK and Fus3/Kss1 MAPK. In this study, the roles of MaOpy2 in Metarhizium acridum were systematically elucidated. The results showed that the MaOpy2 disruption significantly reduced fungal tolerances to UV, heat shock and cell-wall-disrupting agents. Bioassays showed that the decreased fungal pathogenicity by topical inoculation mainly resulted from the impaired penetration ability. However, the growth ability of ΔMaOpy2 was enhanced in insect hemolymph. Importantly, MaOpy2 deletion could significantly increase the conidial yield of M. acridum by shifting the conidiation pattern from normal conidiation to microcycle conidiation on the 1/4SDAY medium. Sixty-two differentially expressed genes (DEGs) during the conidiation pattern shift, including 37 up-regulated genes and 25 down-regulated genes in ΔMaOpy2, were identified by RNA-seq. Further analysis revealed that some DEGs were related to conidiation and hyphal development. This study will provide not only the theoretical basis for elucidating the regulation mechanism for improving the conidial yield and quality in M. acridum but also theoretical guidance for the molecular improvement of entomopathogenic fungi.

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“…In previous work, we found additional evidence that membrane trafficking events that drive cell growth generate signals that are correlated with growth, which could be used to measure growth. For example, delivery of vesicles to the plasma membrane in growing daughter buds generates signals that lead to phosphorylation of the kinase Pkc1 as well as two related kinases called Gin4 and Hsl1 ( Anastasia et al, 2012 ; Jasani et al, 2020 ). In each case, multi-site phosphorylation of these kinases appears to gradually increase during bud growth, and phosphorylation is dependent upon growth and correlated with the extent of growth.…”

Section: Discussionmentioning

confidence: 99%

Growth-dependent signals drive an increase in early G1 cyclin concentration to link cell cycle entry with cell growth

Sommer

DeWitt

Tan

et al. 2021

eLife

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Entry into the cell cycle occurs only when sufficient growth has occurred. In budding yeast, the cyclin Cln3 is thought to initiate cell cycle entry by inactivating a transcriptional repressor called Whi5. Growth-dependent changes in the concentrations of Cln3 or Whi5 have been proposed to link cell cycle entry to cell growth. However, there are conflicting reports regarding the behavior and roles of Cln3 and Whi5. Here, we found no evidence that changes in the concentration of Whi5 play a major role in controlling cell cycle entry. Rather, the data suggest that cell growth triggers cell cycle entry by driving an increase in the concentration of Cln3. We further found that accumulation of Cln3 is dependent upon homologs of mammalian SGK kinases that control cell growth and size. Together, the data are consistent with models in which Cln3 is a crucial link between cell growth and the cell cycle.

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Growth-Dependent Activation of Protein Kinases Suggests a Mechanism for Measuring Cell Growth

Cited by 12 publications

References 72 publications

Determining growth rates from bright-field images of budding cells through identifying overlaps

Determining growth rates from bright-field images of budding cells through identifying overlaps

MaOpy2, a Transmembrane Protein, Is Involved in Stress Tolerances and Pathogenicity and Negatively Regulates Conidial Yield by Shifting the Conidiation Pattern in Metarhizium acridum

Growth-dependent signals drive an increase in early G1 cyclin concentration to link cell cycle entry with cell growth

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