The pheromone-induced nuclear accumulation of the Fus3 MAPK in yeast depends on its phosphorylation state and on Dig1 and Dig2

Blackwell, Ernest; Kim, Hye Jin N; Stone, David E.

doi:10.1186/1471-2121-8-44

Cited by 23 publications

(19 citation statements)

References 83 publications

(95 reference statements)

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“…In S. cerevisiae, Fus3 localization and activation is controlled by a negative feedback loop regulated by Dig1, Dig2, and the phosphatase Msg5. Phosphorylation of Fus3 in response to pheromone treatment results in increased nuclear localization mediated in part by Dig1 and Dig2, but which is antagonized by dephosphorylation of Fus3p by Msg5p (29). We predict similar negative feedback loops also function in the regulation of MAK-2 kinase activity and localization in N. crassa (Fig.…”

Section: Discussionmentioning

confidence: 70%

Oscillatory recruitment of signaling proteins to cell tips promotes coordinated behavior during cell fusion

Fleißner

Leeder

Roca

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

149

235

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Cell-cell communication is essential for coordinating physiological responses in multicellular organisms and is required for various developmental processes, including cell migration, differentiation, and fusion. To facilitate communication, functional differences are usually required between interacting cells, which can be established either genetically or developmentally. However, genetically identical cells in the same developmental state are also capable of communicating, but must avoid self-stimulation. We hypothesized that such cells must alternate their physiological state between signal sending and receiving to allow recognition and behavioral changes. To test this hypothesis, we studied cell communication in the filamentous fungus Neurospora crassa, a simple and experimentally amenable model system. In N. crassa, germinating asexual spores (germlings) of identical genotype chemotropically sense others in close proximity, show attraction-mediated directed growth, and ultimately undergo cell fusion. Here, we report that two proteins required for cell fusion, a MAP kinase (MAK-2) and a protein of unknown molecular function (SO), exhibit rapid oscillatory recruitment to the plasma membranes of interacting germlings undergoing chemotropic interactions via directed growth. Using an inhibitable MAK-2 variant, we show that MAK-2 kinase activity is required both for chemotropic interactions and for oscillation of MAK-2 and SO to opposing cell tips. Thus, N. crassa germlings undergoing chemotropic interactions rapidly alternate between two different physiological states, associated with signal delivery and response. Such spatiotemporal coordination of signaling allows genetically identical and developmentally equivalent cells to avoid self-stimulation and to coordinate their behavior to achieve the beneficial physiological outcome of cell fusion.chemotropism ͉ MAPK ͉ Neurospora

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Section: Discussionmentioning

confidence: 70%

Oscillatory recruitment of signaling proteins to cell tips promotes coordinated behavior during cell fusion

Fleißner

Leeder

Roca

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

149

235

View full text Add to dashboard Cite

show abstract

“…A partial alteration of this D-motif (i.e., replacing the positively charged residues with negatively charged residues) reduces the ability of the Gpa1 subunit to interact with FUS3 and to adapt the responsiveness to mating pheromone (72). The altered D-motif prevents Gpa1 from reducing the nuclear to cytoplasmic ratio of FUS3 during mating responses suggesting Gpa1 uses the D-motif to retain FUS3 in the cytoplasm (73). …”

Section: Erk Specificity In G Protein Signaling Pathwaysmentioning

confidence: 99%

MAPKs in development: insights from Dictyostelium signaling pathways

Hadwiger

Nguyen

2011

BioMolecular Concepts

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Mitogen activated protein kinases (MAPKs) play important roles in the development of eukaryotic organisms through the regulation of signal transduction pathways stimulated by external signals. MAPK signaling pathways have been associated with the regulation of cell growth, differentiation, and chemotaxis, indicating MAPKs contribute to a diverse set of developmental processes. In most eukaryotes, the diversity of external signals is likely to far exceed the diversity of MAPKs, suggesting that multiple signaling pathways might share MAPKs. Do different signaling pathways converge before MAPK function or can MAPKs maintain signaling specificity through interactions with specific proteins? The genetic and biochemical analysis of MAPK pathways in simple eukaryotes such as Dictyostelium offers opportunities to investigate functional specificity of MAPKs in G protein-mediated signal transduction pathways. This review considers the regulation and specificity of MAPK function in pathways that control Dictyostelium growth and development.

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“… 1 After fitting of the whole HOG module to data for wild-type cells, only parameters k 30 and Ki 30 were adjusted to fit data for the fps1 −Δ 1 mutant . 2 Maximal transcriptional induction was set to 10–15 mRNA molecules per cell for all modeled transcription reactions (von der Haar, 2008) . 3 Parameter set in such a way that V ste2_production = [ste2 0 ]· k 4 , so if [Alpha_in_culture] = 0, then [Ste2_0] is the steady-state value . 4 Parameters k nuc_imp and k nuc_exp are set in such a way that steady-state distribution of Fus3 between nucleus and cytoplasm is

\frac{textititalicFus {textititalic3}_{textititalicnuc}}{textititalicFus {textititalic3}_{textititaliccyt}} = 1.4

(Blackwell et al, 2003) . 5 Parameter for nuclear export of Fus3PP is set at k small · k nuc_exp to reflect more efficient nuclear retention of the phosphorylated species (van Drogen et al, 2001; Blackwell et al, 2003, 2007) .…”

Section: Methodsmentioning

confidence: 99%

Cell-to-cell communication circuits: quantitative analysis of synthetic logic gates

Hoffman-Sommer¹

2012

Front. Physio.

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One of the goals in the field of synthetic biology is the construction of cellular computation devices that could function in a manner similar to electronic circuits. To this end, attempts are made to create biological systems that function as logic gates. In this work we present a theoretical quantitative analysis of a synthetic cellular logic-gates system, which has been implemented in cells of the yeast Saccharomyces cerevisiae (Regot et al., 2011). It exploits endogenous MAP kinase signaling pathways. The novelty of the system lies in the compartmentalization of the circuit where all basic logic gates are implemented in independent single cells that can then be cultured together to perform complex logic functions. We have constructed kinetic models of the multicellular IDENTITY, NOT, OR, and IMPLIES logic gates, using both deterministic and stochastic frameworks. All necessary model parameters are taken from literature or estimated based on published kinetic data, in such a way that the resulting models correctly capture important dynamic features of the included mitogen-activated protein kinase pathways. We analyze the models in terms of parameter sensitivity and we discuss possible ways of optimizing the system, e.g., by tuning the culture density. We apply a stochastic modeling approach, which simulates the behavior of whole populations of cells and allows us to investigate the noise generated in the system; we find that the gene expression units are the major sources of noise. Finally, the model is used for the design of system modifications: we show how the current system could be transformed to operate on three discrete values.

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The pheromone-induced nuclear accumulation of the Fus3 MAPK in yeast depends on its phosphorylation state and on Dig1 and Dig2

Cited by 23 publications

References 83 publications

Oscillatory recruitment of signaling proteins to cell tips promotes coordinated behavior during cell fusion

Oscillatory recruitment of signaling proteins to cell tips promotes coordinated behavior during cell fusion

MAPKs in development: insights from Dictyostelium signaling pathways

Cell-to-cell communication circuits: quantitative analysis of synthetic logic gates

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