Mitogen-activated protein kinase regulation of the phosphodiesterase RegA in early Dictyostelium development

Adhikari, Nirakar; Kuburich, Nick A.; Hadwiger, Jeffrey A.

doi:10.1099/mic.0.000868

Cited by 7 publications

(8 citation statements)

References 56 publications

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“…Chemorepulsion is the movement of cells away from a signal. Signals such as ephrin and slit cause repulsion of neuronal growth cones and dendritic spines (Lisabeth, Falivelli, and Pasquale 2013;Adhikari, Kuburich, and Hadwiger 2020;Goldberg et al 2013;Havlioglu et al 2002;Hu 1999;Nguyen Ba-Charvet et al 1999;Pilling et al 2019). For amoeboid cells such as neutrophils, compared to chemoattraction, relatively little is known about chemorepulsion (Pilling et al 2019;Herlihy et al 2015;Herlihy et al 2013;Herlihy et al 2017;White et al 2018).…”

Section: Introductionmentioning

confidence: 99%

A chemorepellent inhibits local Ras activation to inhibit pseudopod formation to bias cell movement away from the chemorepellent

Kirolos

Gomer

2022

MBoC

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The ability of cells to sense chemical gradients is essential during development, morphogenesis, and immune responses. Although much is known about chemoattraction, chemorepulsion remains poorly understood. Proliferating Dictyostelium cells secrete a chemorepellent protein called AprA. AprA prevents pseudopod formation at the region of the cell closest to the source of AprA, causing the random movement of cells to be biased away from the AprA. Activation of Ras proteins in a localized sector of a cell cortex helps to induce pseudopod formation, and Ras proteins are needed for AprA chemorepulsion. Here we show that AprA locally inhibits Ras cortical activation through the G protein-coupled receptor GrlH, the G protein subunits Gβ and Gα8, Ras protein RasG, protein kinase B, the p-21 activated kinase PakD, and the extracellular signal-regulated kinase Erk1. Diffusion calculations and experiments indicate that in a colony of cells, high extracellular concentrations of AprA in the center can globally inhibit Ras activation, while a gradient of AprA that naturally forms at the edge of the colony allow cells to activate Ras at sectors of the cell other than the sector of the cell closest to the center of the colony, effectively inducing both repulsion from the colony and cell differentiation. Together, these results suggest that a pathway that inhibits local Ras activation can mediate chemorepulsion. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text]

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Section: Introductionmentioning

confidence: 99%

A chemorepellent inhibits local Ras activation to inhibit pseudopod formation to bias cell movement away from the chemorepellent

Kirolos

Gomer

2022

MBoC

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“…Manta v 1.6.0 was used to call somatic variants in each mutant strain using the appropriate control strain as the ‘normal’ sample [ 36 ]. Samtools v 1.15 was used to filter cram files to remove duplicate reads, keep only paired reads with primary alignments with scores [ 37 ]. Samtools, Bedtools v 2.30.0, and custom R script v 4.1.0 was used to extract reads in which one member of the pair was mapped to the plasmid and the other is mapped to the reference genome (chimeric read pairs) [ 38 , 39 ].…”

Section: Methodsmentioning

confidence: 99%

Copine C plays a role in adhesion and streaming in Dictyostelium

Nichols,

Ide,

Morrison

et al. 2024

Cell Adhesion & Migration

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Copines are a family of calcium-dependent membrane-binding proteins. To study these proteins, anull mutant for cpnC was created in Dictyostelium , which has six copines genes ( cpnA-cpnF ). During development, cpnC − cells were able to aggregate, but did not form streams. Once aggregated into mounds, they formed large ring structures. cpnC − cells were less adherent to plastic substrates, but more adherent to other cells. These phenotypes correlated with changes in adhesion protein expression with decreased expression of SibA and increased expression of CsaA in developing cpnC − cells. We also measured the expression of RegA, a cAMP phosphodiesterase, and found that cpnC − cells have reduced RegA expression. The reduced RegA expression in cpnC − cells is most likely responsible for the observed phenotypes.

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“…Despite D. discoideum being an evolutionarily distant organism from humans, its genome encodes conserved orthologs of human proteins associated with cancer. [ 38–42 ] Furthermore, D. discoideum presents the opportunity to study the function of cancer genes in the absence of the tumor suppressor p53, as the organism diverged from unikonts prior to the appearance of p53 in choanoflagellates. [ 43 ] Perhaps the most well studied tumor suppressor after p53 is phosphatase and tensin homolog (PTEN), which is commonly mutated or deleted in cancer.…”

Section: How Can D Discoideum Be Used To Study Genes Associated Withmentioning

confidence: 99%

Cancer and the breakdown of multicellularity: What Dictyostelium discoideum, a social amoeba, can teach us

et al. 2021

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Ancient pathways promoting unicellularity and multicellularity are associated with cancer, the former being pro‐oncogenic and the latter acting to suppress oncogenesis. However, there are only a limited number of non‐vertebrate models for studying these pathways. Here, we review Dictyostelium discoideum and describe how it can be used to understand these gene networks. D. discoideum has a unicellular and multicellular life cycle, making it possible to study orthologs of cancer‐associated genes in both phases. During development, differentiated amoebae form a fruiting body composed of a mass of spores that are supported atop a stalk. A portion of the cells sacrifice themselves to become non‐reproductive stalk cells. Cheating disrupts the principles of multicellularity, as cheater cells alter their cell fate to preferentially become spores. Importantly, D. discoideum has gene networks and several strategies for maintaining multicellularity. Therefore, D. discoideum can help us better understand how conserved genes and pathways involved in multicellularity also influence cancer development, potentially identifying new therapeutic avenues.

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Mitogen-activated protein kinase regulation of the phosphodiesterase RegA in early Dictyostelium development

Cited by 7 publications

References 56 publications

A chemorepellent inhibits local Ras activation to inhibit pseudopod formation to bias cell movement away from the chemorepellent

A chemorepellent inhibits local Ras activation to inhibit pseudopod formation to bias cell movement away from the chemorepellent

Copine C plays a role in adhesion and streaming in Dictyostelium

Cancer and the breakdown of multicellularity: What Dictyostelium discoideum, a social amoeba, can teach us

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