dictyNews

Electronic Edition

Volume 47, number 19

September 24, 2021



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Abstracts

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MAPK docking motif in the Dictyostelium Ga2 subunit is required 

for aggregation and transcription factor translocation

 

Nirakar Adhikari, Imani N. McGill, and Jeffrey A. Hadwiger



Department of Microbiology and Molecular Genetics, 

Oklahoma State University, Stillwater, OK 74078-3020

 



Cellular Signalling, in press

      

Some G protein alpha subunits contain a mitogen-activated protein 

kinase (MAPK) docking motif (D-motif) near the amino terminus 

that can impact cellular responses to external signals. The 

Dictyostelium Ga2 G protein subunit is required for chemotaxis 

to cAMP during the onset of multicellular development and this 

subunit contains a putative D-motif near the amino terminus. The 

Ga2 subunit D-motif was altered to examine its potential role in 

chemotaxis and multicellular development. In ga2- cells the 

expression of the D-motif mutant (Ga2D-) or wild-type subunit 

from high copy number vectors rescued cell aggregation but 

blocked the transition of mounds into slugs. This phenotype was 

also observed in parental strains with a wild-type ga2 locus 

indicating that the heterologous Ga2 subunit expression interferes 

with multicellular morphogenesis. Expression of the Ga2D- subunit 

from a low copy number vectors in ga2- cells did not rescue 

aggregation whereas the wild-type Ga2 subunit rescued aggregation 

efficiently and allowed wild-type morphological development. The 

Ga2D- and Ga2 subunit were both capable of restoring comparable 

levels of cAMP stimulated motility and the ability to co-aggregate 

with wild-type cells implying that the aggregation defect of Ga2D- 

expressing cells is due to insufficient intercellular signaling. 

Expression of the Ga2 subunit but not the Ga2D- subunit fully 

restored the ability of cAMP to stimulate the translocation of the 

GtaC transcription factor suggesting the D-motif is important for 

transcription factor regulation. These results suggest that the 

D-motif of Ga2 plays a role in aggregation and other developmental 

responses involved with cAMP signaling.





submitted by: Jeff Hadwiger [[log in to unmask]]

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Interactome and evolutionary conservation of Dictyostelid small 

Gtpases and their direct regulators



Gillian Forbes1, Christina Schilde1, Hajara Lawal1, Koryu Kin1,2, 

Qingyou Du1, Zhi-hui Chen1, Francisco Rivero3* and Pauline Schaap1*



1School of Life Sciences, University of Dundee, MSI/WTB complex, 

Dundee DD15EH, UK.



2Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), 

Passeig Marítim de la Barceloneta 37-49, 08003 Barcelona, Spain

3Centre for Atherothrombosis and Metabolic Disease, Hull York 

Medical School, Faculty of Health Sciences, University of Hull, 

HU67RX, Hull.





Small GTPases, in press



The GTP binding proteins known as small GTPases make up one 

of the largest groups of regulatory proteins and control almost all 

functions of living cells. Their activity is under respectively 

positive and negative regulation by guanine nucleotide exchange 

factors (GEFs) and GTPase activating proteins (GAPs), which together 

with their upstream regulators and the downstream targets of the 

small GTPases form formidable signaling networks. While genomics 

has revealed the large size of the GTPase, GEF and GAP repertoire, 

only a small fraction of their interactions and functions have yet been 

experimentally explored. Dictyostelid social amoebas have been 

particularly useful in unraveling the roles of many proteins in the 

Rac-Rho and Ras-Rap families of GTPases in directional cell migration 

and regulation of the actin cytoskeleton. Almost completely assembled 

genomes and cell-type specific and developmental transcriptomes 

are available for Dictyostelium species that span the 0.5 billion years 

of evolution of the group from their unicellular ancestor. In this 

work, we identified all GTPases, GEFs and GAPs from genomes 

representative of the four major taxon groups and investigated their 

phylogenetic relationships and evolutionary conservation and change 

in their functional domain architecture and in their developmental 

and cell-type specific expression. We performed hierarchical cluster 

analysis of the expression profiles of the ~2000 analysed genes to 

identify putative interacting sets of GTPases, GEFs and GAPs, which 

highlighted sets known to interact experimentally and many novel 

combinations. The work represents a valuable resource for research 

into all fields of cellular regulation.





submitted by: Pauline Schaap [[log in to unmask]]

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Using Dictyostelium to Advance Our Understanding of the Role 

of Medium Chain Fatty Acids in Health and Disease



Erwann Pain, Sonia Shinhmar and Robin S. B. Williams



Centre for Biomedical Sciences, School of Biological Sciences, 

Royal Holloway University of London, Egham, United Kingdom





Frontiers in Cell and Developmental Biology

doi: 10.3389/fcell.2021.722066



Ketogenic diets have been utilized for many years to improve health,

 and as a dietary approach for the treatment of a range of diseases, 

 where the mechanism of these low carbohydrate and high fat diets is 

 widely considered to be through the production of metabolic products 

 of fat breakdown, called ketones. One of these diets, the medium 

 chain triglyceride ketogenic diet, involves high fat dietary intake 

 in the form of medium chain fatty acids (MCFAs), decanoic and 

 octanoic acid, and is commonly used in endurance and high intensity 

 exercises but has also demonstrated beneficial effects in the 

 treatment of numerous pathologies including drug resistant epilepsy, 

 cancer, and diabetes. Recent advances, using Dictyostelium discoideum 

 as a model, have controversially proposed several direct molecular 

 mechanisms for decanoic acid in this diet, independent of ketone 

 generation. Studies in this model have identified that decanoic acid 

 reduces phosphoinositide turnover, diacylglycerol kinase (DGK) a

 ctivity, and also inhibits the mechanistic target of rapamycin 

 complex 1 (mTORC1). These discoveries could potentially impact the 

 treatment of a range of disorders including epilepsy, cancer and 

 bipolar disorder. In this review, we summarize the newly proposed 

 mechanisms for decanoic acid, identified using D. discoideum, and 

 highlight potential roles in health and disease treatment.





submitted by: Robin Williams [[log in to unmask]]

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[End dictyNews, volume 47, number 19]