Quantitative variations of ADF/cofilin’s multiple actions on actin filaments with pH

Wioland, Hugo; Jégou, Antoine; Romet-Lemonne, Guillaume

doi:10.1101/422824

Cited by 2 publications

(1 citation statement)

References 46 publications

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“…Ipl1 kinase mediated phosphorylation of Dam1 S23 directly inhibits attachment of the kinetochore to the microtubules and Cla4/Ste20/Ypk2 mediated phosphorylation of Myo5 S357 is required for polarization of the actin cytoskeleton. Interestingly, pH changes have been associated with modulation of cell cycle (Orij et al, 2012) and actin polymerization (Wioland et al, 2019), which is likely induced by the stress response defined in cluster 2. We identified 57 phosphosites that showed selective regulation in one of the perturbation clusters (Figure 5D, Table S7).…”

Section: Perturbation-specific Phosphorylation Response Programsmentioning

confidence: 99%

The regulatory landscape of the yeast phosphoproteome

Leutert

Barente

Fukuda

et al. 2022

Preprint

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The cellular ability to react to environmental fluctuations depends on signaling networks that are controlled by the dynamic activities of kinases and phosphatases. To gain insight into these stress-responsive phosphorylation networks, we generated a quantitative mass spectrometry-based atlas of early phosphoproteomic responses in Saccharomyces cerevisiae exposed to 101 environmental and chemical perturbations. We report phosphosites on 59% of the yeast proteome, with 18% of the proteome harboring a phosphosite that is regulated within 5 minutes of stress exposure. We identify shared and perturbation-specific stress response programs, uncover dephosphorylation as an integral early event, and dissect the interconnected regulatory landscape of kinase-substrate networks, as we exemplify with TOR signaling. We further reveal functional organization principles of the stress-responsive phosphoproteome based on phosphorylation site motifs, kinase activities, subcellular localizations, shared functions, and pathway intersections. This information-rich map of 25,000 regulated phosphosites advances our understanding of signaling networks.

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Section: Perturbation-specific Phosphorylation Response Programsmentioning

confidence: 99%

The regulatory landscape of the yeast phosphoproteome

Leutert

Barente

Fukuda

et al. 2022

Preprint

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The non–muscle actinopathy–associated mutation E334Q in cytoskeletal γ– actin perturbs interaction of actin filaments with myosin and ADF/cofilin family proteins

Greve,

Marquardt,

Heiringhoff

et al. 2023

Preprint

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Various heterozygous cytoskeletal γ–actin mutations have been shown to cause Baraitser–Winter cerebrofrontofacial syndrome, non–syndromic hearing loss, or isolated eye coloboma. Here, we report the biochemical characterization of human cytoskeletal γ–actin carrying mutation E334Q, a mutation that leads to a hitherto unspecified non–muscle actinopathy. Following expression, purification, and removal of linker and thymosin β4 tag sequences, the p.E334Q monomers show normal integration into linear and branched actin filaments. The mutation does not affect thermal stability, actin filament nucleation, elongation and turnover. Model building and normal mode analysis predict significant differences in the interaction of p.E334Q–filaments with myosin motors and members of the ADF/cofilin family of actin–binding proteins. Assays probing the interactions of p.E334Q–filaments with human class 2 and class 5 myosin motor constructs show significant reductions in sliding velocity and actin–affinity. E334Q differentially affects cofilin-mediated actin dynamics by increasing the rate of cofilin-mediatedde novonucleation of actin filaments and decreasing the efficiency of cofilin-mediated filament severing. Thus, it is likely that p.E334Q-mediated changes in myosin motor activity, as well as filament turnover contribute to the observed disease phenotype.

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Quantitative variations of ADF/cofilin’s multiple actions on actin filaments with pH

Cited by 2 publications

References 46 publications

The regulatory landscape of the yeast phosphoproteome

The regulatory landscape of the yeast phosphoproteome

The non–muscle actinopathy–associated mutation E334Q in cytoskeletal γ– actin perturbs interaction of actin filaments with myosin and ADF/cofilin family proteins

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