The Cellular and Developmental Roles of Cullins, Neddylation, and the COP9 Signalosome in Dictyostelium discoideum

IntroductionFree-living amoebae of the Naegleria genus belong to the major protist clade Heterolobosea and are ubiquitously distributed in soil and freshwater habitats. Of the 47 Naegleria species described, N. fowleri is the only one being pathogenic to humans, causing a rare but fulminant primary amoebic meningoencephalitis. Some Naegleria genome sequences are publicly available, but the genetic basis for Naegleria diversity and ability to thrive in diverse environments (including human brain) remains unclear.MethodsHerein, we constructed a high-quality Naegleria genus pangenome to obtain a comprehensive catalog of genes encoded by these amoebae. For this, we first sequenced, assembled, and annotated six new Naegleria genomes.Results and DiscussionGenome architecture analyses revealed that Naegleria may use genome plasticity features such as ploidy/aneuploidy to modulate their behavior in different environments. When comparing 14 near-to-complete genome sequences, our results estimated the theoretical Naegleria pangenome as a closed genome, with 13,943 genes, including 3,563 core and 10,380 accessory genes. The functional annotations revealed that a large fraction of Naegleria genes show significant sequence similarity with those already described in other kingdoms, namely Animalia and Plantae. Comparative analyses highlighted a remarkable genomic heterogeneity, even for closely related strains and demonstrate that Naegleria harbors extensive genome variability, reflected in different metabolic repertoires. If Naegleria core genome was enriched in conserved genes essential for metabolic, regulatory and survival processes, the accessory genome revealed the presence of genes involved in stress response, macromolecule modifications, cell signaling and immune response. Commonly reported N. fowleri virulence-associated genes were present in both core and accessory genomes, suggesting that N. fowleri’s ability to infect human brain could be related to its unique species-specific genes (mostly of unknown function) and/or to differential gene expression. The construction of Naegleria first pangenome allowed us to move away from a single reference genome (that does not necessarily represent each species as a whole) and to identify essential and dispensable genes in Naegleria evolution, diversity and biology, paving the way for further genomic and post-genomic studies.

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“…Herein, we detected 9 genes of the cullin family of proteins. Cullin proteins were also detected in Dictyostelium ( Kim et al, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

Naegleria genus pangenome reveals new structural and functional insights into the versatility of these free-living amoebae

et al. 2023

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“…COP9 signalosome (CSN) and NEDD8 protease 1 (NEDP1), which release substrates and NEDD8 (Fig. 2 ) [ 123 , 124 ]. In 2022, A study demonstrated that PML/RARα fusion proteins that drive chromosomal translocation production in acute promyelocytic leukemia (APL) are assembled by LLPS into nucleosomal structures.…”

Section: Ptms Of Proteins Related To Eukaryotic Phase Separationmentioning

confidence: 99%

Crosstalk between protein post-translational modifications and phase separation

Liu,

Feng,

Wang

et al. 2024

Cell Commun Signal

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The phenomenon of phase separation is quite common in cells, and it is involved in multiple processes of life activities. However, the current research on the correlation between protein modifications and phase separation and the interference with the tendency of phase separation has some limitations. Here we focus on several post-translational modifications of proteins, including protein phosphorylation modification at multiple sites, methylation modification, acetylation modification, ubiquitination modification, SUMOylation modification, etc., which regulate the formation of phase separation and the stability of phase separation structure through multivalent interactions. This regulatory role is closely related to the development of neurodegenerative diseases, tumors, viral infections, and other diseases, and also plays essential functions in environmental stress, DNA damage repair, transcriptional regulation, signal transduction, and cell homeostasis of living organisms, which provides an idea to explore the interaction between novel protein post-translational modifications and phase separation.

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“…The CSN signalosome complex supports numerous developmental events in eukaryotes, partly by facilitating ubiquitin-dependent degradation of aged, misfolded, and mislocalized proteins and promoting ubiquitin homeostasis (Kim et al, 2022). For example, studies have shown that selected subunits of the CSN complex directly interact with the 19S regulatory unit of the 26S proteasome complex in plants and animals (Yu et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

COP9 signalosome complex subunit-7-mediated regulation of cAMP levels contributes to autophagic degradation and pathogenesis of rice blast fungusMagnaporthe oryzae

Lin

Guo

Batool

et al. 2023

Preprint

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Photo-dependent processes, including circadian rhythm, autophagy, ubiquitination, neddylation/deneddylation, and metabolite biosynthesis, profoundly influence microbial Although a photomorphogenesis signalosome (COP9/CSN) has been identified, the mechanism by which this large complex contributes to pathophysiological processes in filamentous fungi remains unclear. Here, we identified eight CSN complex subunits in the rice blast fungusMagnaporthe oryzaeand functionally characterized the translocon subunits containing a nuclear export or localization signal (NES/NLS). Targeted gene replacement of these CSN subunits, includingMoCSN3,MoCSN5,MoCSN6,MoCSN7, andMoCSN12, attenuated vegetative growth and conidiation inM. oryzaeand rendered non-pathogenic deletion strains.MoCSN7deletion significantly suppressed arachidonic acid catabolism, compromised cell wall integrity, subverted photo-dependent ubiquitination, and abolished photo-responsiveness. Surprisingly, we also discovered that MoCSN subunits, particularly Mosn7, are required for the cAMP-dependent regulation of autophagic flux. Therefore, MoCSN significantly contributes to morphological, physiological, and pathogenic differentiation inM. oryzaeby fostering cross-talk between multiple pathways.

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The Cellular and Developmental Roles of Cullins, Neddylation, and the COP9 Signalosome in Dictyostelium discoideum

Cited by 6 publications

References 169 publications

Naegleria genus pangenome reveals new structural and functional insights into the versatility of these free-living amoebae

Naegleria genus pangenome reveals new structural and functional insights into the versatility of these free-living amoebae

Crosstalk between protein post-translational modifications and phase separation

COP9 signalosome complex subunit-7-mediated regulation of cAMP levels contributes to autophagic degradation and pathogenesis of rice blast fungusMagnaporthe oryzae

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