Extracellular polyphosphate signals through Ras and Akt to prime <i>Dictyostelium discoideum</i> cells for development

Suess, Patrick M.; Watson, Jacob; Chen, Wensheng; Gomer, Richard H.

doi:10.1242/jcs.203372

Cited by 39 publications

(50 citation statements)

References 65 publications

(98 reference statements)

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“…Due to its multicellular cycle, D. discoideum , referred to as a social amoeba, is used as a model to study aspects of development including intercellular signaling ( 27 ) [reviewed in Ref. ( 22 )], quorum sensing ( 28 ), cell–cell recognition ( 29 ), cell fate determination ( 30 ), tissue patterning ( 31 ), and even societal concepts such as cooperativity and altruism ( 32 ).…”

Section: Dictyostelium Discoideummentioning

confidence: 99%

Eat Prey, Live: Dictyostelium discoideum As a Model for Cell-Autonomous Defenses

et al. 2018

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The soil-dwelling social amoeba Dictyostelium discoideum feeds on bacteria. Each meal is a potential infection because some bacteria have evolved mechanisms to resist predation. To survive such a hostile environment, D. discoideum has in turn evolved efficient antimicrobial responses that are intertwined with phagocytosis and autophagy, its nutrient acquisition pathways. The core machinery and antimicrobial functions of these pathways are conserved in the mononuclear phagocytes of mammals, which mediate the initial, innate-immune response to infection. In this review, we discuss the advantages and relevance of D. discoideum as a model phagocyte to study cell-autonomous defenses. We cover the antimicrobial functions of phagocytosis and autophagy and describe the processes that create a microbicidal phagosome: acidification and delivery of lytic enzymes, generation of reactive oxygen species, and the regulation of Zn2+, Cu2+, and Fe2+ availability. High concentrations of metals poison microbes while metal sequestration inhibits their metabolic activity. We also describe microbial interference with these defenses and highlight observations made first in D. discoideum. Finally, we discuss galectins, TNF receptor-associated factors, tripartite motif-containing proteins, and signal transducers and activators of transcription, microbial restriction factors initially characterized in mammalian phagocytes that have either homologs or functional analogs in D. discoideum.

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Section: Dictyostelium Discoideummentioning

confidence: 99%

Eat Prey, Live: Dictyostelium discoideum As a Model for Cell-Autonomous Defenses

et al. 2018

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“…Thus, we examined polyphosphate levels in the tert KO because of their known importance to developmental timing in Dictyostelium [66]. We stained the CM with DAPI for 5 mins and checked the polyphosphate specific fluorescence using a spectrofluorometer.…”

Section: Resultsmentioning

confidence: 99%

“…A line ending in an arrowhead suggests that the first element directly or indirectly promotes the activity or levels of the second; inhibition is suggested by a line ending in a cross-bar. Published works that report on the nature of each pathway within the network are as follows: a[29], [40]; b[29]; c[66]; d[52], [53], [54]; e[61], [82], [83], [84]; f[85]; g [86], [87]; h[88–90]; i[91], [33]; j[77]; k[92], [93], [94]; l[26], [39]; m[27]; n[35]; o[95], [96]; p[67]; q[67], [75]; r[67]; s[97]; t[75]; u[65]; v[98], [39]; w[99], [100]; x[66]; y[101].…”

Section: Introductionmentioning

confidence: 99%

A telomerase with novel non-canonical roles: TERT controls cellular aggregation and tissue size inDictyostelium

Nassir

Hyde

Baskar

2019

Preprint

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11Telomerase, particularly its main subunit, the reverse transcriptase, TERT, prevents DNA 12 erosion during eukaryotic chromosomal replication, but also has poorly understood non-13 canonical functions. Here, in the model social amoeba Dictyostelium discoideum, we show 14 that the protein encoded by tert has telomerase-like motifs and regulates, non-canonically, 15 important developmental processes. Expression levels of wild-type (WT) tert were biphasic, 16 peaking at 8 and 12 h post-starvation, aligning with developmental events, such as the 17 initiation of streaming (~7 h) and mound formation (~10 h). In tert KO mutants, however, 18 aggregation was delayed until 16 h. Large, irregular streams formed, then broke up, leading 19 to small mounds. The mound-size defect was not induced when a KO mutant of countin (a 20 master size-regulating gene) was treated with TERT inhibitors but anti-countin antibodies did 21 rescue size in the tert KO. Further, conditioned medium from countin mutants failed to 22 rescue size in the tert KO, but the converse experiment worked. These and additional 23 the migration of cells that form each fruiting body is delayed and irregular. These results are 48 significant because they show, for the first time, that a telomerase can influence cell 49 migration and tissue size regulation, two processes involved in a wide range of cancers. 50 51 Introduction 52 Each time a chromosome replicates, it loses some DNA from each of its ends. This is not 53 necessarily problematic, because the chromosome is initially capped at each end by a 54 sacrificial strand of non-coding DNA, a telomere [1][2][3]. Further instances of replication, 55 however, can expose the coding DNA, unless the cell can keep repairing the shortened 56 telomeres, by the action of the enzyme complex, telomerase. Accordingly, telomerase, whose 57 main subunits comprise a reverse transcriptase (TERT), and the telomerase RNA component 58 (TERC) [4], has much significance in the biology and pathology of multicellular organisms. 59As somatic tissues age, for example, telomerase is downregulated, and the resulting telomeric 60 dysfunction can lead to chromosomal instability and various pathologies, including disrupted 61 pregnancies and cancer [5][6][7]. In other cases, the upregulation of telomerase is also associated 62 with, and a biomarker of, some cancers, because it allows the unchecked proliferation of 63 immortalised tumour cells [6, 8]. Telomerase also has many non-canonical roles, in which 64 telomere maintenance, or even telomerase activity, is not required [9, 10]. For example, 65 telomerase is known to have non-canonical roles in neuronal differentiation [11], RNA 66 silencing [12], enhanced mitochondrial function [13] and various cancers [9, 14]. 67Our understanding of telomeres and telomerase began, and has continued to develop, through 68 the study of model organisms such as Drosophila, Zea mays, Tetrahymena, yeast and mice 69 [2, 3,[15][16][17][18][19]]. One model system in which the possible roles of telomerase hav...

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“…In addition to its intracellular effects on D. discoideum development, excreted polyphosphate also promotes development by inhibiting proliferation and signaling through Ras and Akt (8, 9). In other model organisms, polyphosphate functions as a chaperone promoting the productive refolding of misfolded proteins and stabilizing amyloid fibers (43, 44).…”

Section: Introductionmentioning

confidence: 99%

A Heat Shock Protein 48 (HSP48) Biomolecular Condensate Is Induced during Dictyostelium discoideum Development

Santarriaga

Fikejs

Scaglione

et al. 2019

mSphere

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The social amoeba Dictyostelium discoideum’s proteome contains a vast array of simple sequence repeats, providing a unique model to investigate proteostasis. Upon conditions of cellular stress, D. discoideum undergoes a developmental process, transitioning from a unicellular amoeba to a multicellular fruiting body. Little is known about how proteostasis is maintained during D. discoideum’s developmental process. Here, we have identified a novel α-crystallin domain-containing protein, heat shock protein 48 (HSP48), that is upregulated during D. discoideum development. HSP48 functions in part by forming a biomolecular condensate via its highly positively charged intrinsically disordered carboxy terminus. In addition to HSP48, the highly negatively charged primordial chaperone polyphosphate is also upregulated during D. discoideum development, and polyphosphate functions to stabilize HSP48. Upon germination, levels of both HSP48 and polyphosphate dramatically decrease, consistent with a role for HSP48 and polyphosphate during development. Together, our data demonstrate that HSP48 is strongly induced during Dictyostelium discoideum development. We also demonstrate that HSP48 forms a biomolecular condensate and that polyphosphate is necessary to stabilize the HSP48 biomolecular condensate. IMPORTANCE During cellular stress, many microbes undergo a transition to a dormant state. This includes the social amoeba Dictyostelium discoideum that transitions from a unicellular amoeba to a multicellular fruiting body upon starvation. In this work, we identify heat shock protein 48 (HSP48) as a chaperone that is induced during development. We also show that HSP48 forms a biomolecular condensate and is stabilized by polyphosphate. The findings here identify Dictyostelium discoideum as a novel microbe to investigate protein quality control pathways during the transition to dormancy.

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Extracellular polyphosphate signals through Ras and Akt to prime Dictyostelium discoideum cells for development

Cited by 39 publications

References 65 publications

Eat Prey, Live: Dictyostelium discoideum As a Model for Cell-Autonomous Defenses

Eat Prey, Live: Dictyostelium discoideum As a Model for Cell-Autonomous Defenses

A telomerase with novel non-canonical roles: TERT controls cellular aggregation and tissue size inDictyostelium

A Heat Shock Protein 48 (HSP48) Biomolecular Condensate Is Induced during Dictyostelium discoideum Development

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