dictyNews

Electronic Edition

Volume 48, number 3

February 11, 2022



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Abstracts

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The cellular and developmental roles of cullins, neddylation, and the 

COP9 signalosome in Dictyostelium discoideum



William D Kim, Sabateeshan Mathavarajah, Robert J Huber



Environmental and Life Sciences Graduate Program, Trent University, 

Peterborough, Ontario, Canada

Department of Pathology, Dalhousie University, Halifax, Nova Scotia,

 Canada

Department of Biology, Trent University, Peterborough, Ontario, 

Canada





Frontiers in Physiology, accepted



Cullins are core components of cullin-RING E3 ubiquitin ligases (CRLs), 

which regulate the degradation, function, and subcellular trafficking of 

proteins. Cullins are post-translationally regulated through neddylation, 

a process that conjugates the ubiquitin-like modifier protein neural 

precursor cell expressed developmentally downregulated protein 8 

(NEDD8) to target cullins, as well as non-cullin proteins. Counteracting 

neddylation is the deneddylase, COP9 signalosome (CSN), which 

removes NEDD8 from target proteins. Recent comparative genomics 

studies revealed that CRLs and the CSN are highly conserved in 

Amoebozoa. A well-studied representative of Amoebozoa, the social 

amoeba Dictyostelium discoideum, has been used for close to 100 

years as a model organism for studying conserved cellular and 

developmental processes due its unique life cycle comprised of 

unicellular and multicellular phases. The organism is also recognized 

as an exceptional model system for studying cellular processes 

impacted by human diseases, including but not limited to, cancer and 

neurodegeneration. Recent work shows that the neddylation inhibitor, 

MLN4924 (Pevonedistat), inhibits growth and multicellular development 

in D. discoideum, which supports previous work that revealed the cullin 

interactome in D. discoideum and the roles of cullins and the CSN in 

regulating cellular and developmental processes during the 

D. discoideum life cycle. Here, we review the roles of cullins, 

neddylation and the CSN in D. discoideum to guide future work on 

using this biomedical model system to further explore the evolutionarily 

conserved functions of cullins and neddylation.





Submitted by Robert Huber [[log in to unmask]]

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A bacterial endosymbiont of the fungus Rhizopus microsporus drives 

phagocyte evasion and opportunistic virulence



H Itabangi1, PCS Sephton-Clark1, DP Tamayo2, X Zhou1, GP Starling3, 

Z Mahamoud3, I Insua4, M Probert1, J Correia1, PJ Moynihan1, 

T Gebremariam5, Y Gu5, AS Ibrahim5,6, GD Brown2, JS King3*, 

ER Ballou1,2* and K Voelz1*



1Institute of Microbiology and Infection, School of Biosciences, University 

of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.

2MRC Centre for Medical Mycology, University of Exeter, Geoffrey Pope 

Building, Stocker Road, Exeter, EX4 4QD

3School of Biosciences, University of Sheffield, Western Bank, Sheffield, 

S10 2TN, UK.

4School of Chemistry, University of Birmingham, Edgbaston, 

Birmingham, B15 2TT, UK.

5The Lundquist Institute for Biomedical Innovation at Harbor-UCLA 

Medical Center, Torrance, California, U.S.A.

6David Geffen School of Medicine, UCLA, Los Angeles, California, U.S.A.





Current Biology, in press

https://doi.org/10.1016/j.cub.2022.01.028



Opportunistic infections by environmental fungi are a growing clinical 

problem, driven by an increasing population of people with 

immunocompromising conditions. Spores of the Mucorales order are 

ubiquitous in the environment but can also cause acute invasive 

infections in humans through germination and evasion of the 

mammalian host immune system. How they achieve this and the 

evolutionary drivers underlying the acquisition of virulence mechanisms 

are poorly understood. Here, we show that a clinical isolate of Rhizopus 

microsporus contains a Ralstonia pickettii bacterial endosymbiont 

required for virulence in both zebrafish and mice and that this 

endosymbiosis enables the secretion of factors that potently suppress 

growth of the soil amoeba Dictyostelium discoideum, as well as their 

ability to engulf and kill other microbes. As amoebas are natural 

environmental predators of both bacteria and fungi, we propose that 

this tri-kingdom interaction contributes to establishing endosymbiosis 

and the acquisition of anti-phagocyte activity. Importantly, we show that 

this activity also protects fungal spores from phagocytosis and clearance 

by human macrophages, and endosymbiont removal renders the fungal 

spores avirulent in vivo. Together, these findings describe a new role 

for a bacterial endosymbiont in Rhizopus microsporus pathogenesis in 

animals and suggest a mechanism of virulence acquisition through 

environmental interactions with amoebas.

 



Submitted by Jason King [[log in to unmask]]

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[End dictyNews, volume 48, number 3]