Regulation of aggregate size and pattern by adenosine and caffeine in cellular slime molds

Jaiswal, Pundrik; Soldati, Thierry; Thewes, Sascha; Baskar, Ramamurthy

doi:10.1186/1471-213x-12-5

Cited by 16 publications

(21 citation statements)

References 59 publications

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“…26,35,[114][115][116][117][118] Furthermore, D. discoideum has also been used to identify and dissect the mechanisms of action of drugs with potential utility in medical therapy against pathogens. [119][120][121][122] M. marinum infects mainly fish and frogs, but it can also produce skin lesions in humans. Due to safety reasons and to the faster growth rate than its close relative M. tuberculosis, 123 M. marinum represents an easier tool to research mycobacterial pathogenesis.…”

Section: Autophagy and Disease: New Leads From The Social Amoeba In Hmentioning

confidence: 99%

Autophagy inDictyostelium: Mechanisms, regulation and disease in a simple biomedical model

et al. 2016

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Autophagy is a fast-moving field with an enormous impact on human health and disease. Understanding the complexity of the mechanism and regulation of this process often benefits from the use of simple experimental models such as the social amoeba Dictyostelium discoideum. Since the publication of the first review describing the potential of D. discoideum in autophagy, significant advances have been made that demonstrate both the experimental advantages and interest in using this model. Since our previous review, research in D. discoideum has shed light on the mechanisms that regulate autophagosome formation and contributed significantly to the study of autophagy-related pathologies. Here, we review these advances, as well as the current techniques to monitor autophagy in D. discoideum. The comprehensive bioinformatics search of autophagic proteins that was a substantial part of the previous review has not been revisited here except for those aspects that challenged previous predictions such as the composition of the Atg1 complex. In recent years our understanding of, and ability to investigate, autophagy in D. discoideum has evolved significantly and will surely enable and accelerate future research using this model.

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Section: Autophagy and Disease: New Leads From The Social Amoeba In Hmentioning

confidence: 99%

Autophagy inDictyostelium: Mechanisms, regulation and disease in a simple biomedical model

et al. 2016

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“…As mentioned previously, adenosine and caffeine are known to alter the cAMP relay [62,63], thereby affecting aggregate size. This occurs in a number of Dictyostelids [33]. We observed enhanced expression of 5’NT in the tert KO (Fig 15A, p=0.0042) suggesting increased adenosine levels (5’NT converts AMP to adenosine).…”

Section: Resultsmentioning

confidence: 62%

“…One of its advantages is that the processes of cell division (i.e. growth) and development are uncoupled [25], making the organism a highly tractable system for the study, in particular, of differentiation and tissue size regulation [26–33]. In culture, when its bacterial food source is abundant, D. discoideum multiplies as single-celled amoebae.…”

Section: Introductionmentioning

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%

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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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“…cAMP levels are regulated, in part, by intracellular (REGA) and extracellular (PDSA and PDE4) phosphodiesterases, degrading excess intracellular and extracellular cAMP, respectively [Faure et al, 1990;Shaulsky et al, 1996;Bader et al, 2006;Garcia et al, 2009]. The organised generation of cAMP pulses and their relay is important for both initiating aggregation and formation of fruiting bodies [Gomer et al, 2011;Jaiswal et al, 2012].…”

Section: Introductionmentioning

confidence: 99%

Poly(ADP‐ribose) polymerase‐1 (PARP‐1) regulates developmental morphogenesis and chemotaxis in Dictyostelium discoideum

Jubin

Kadam

Begum

2019

Biology of the Cell

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Background information Poly(ADP‐ribose) polymerase‐1 (PARP‐1) has been attributed to varied roles in DNA repair, cell cycle, cell death, etc. Our previous reports demonstrate the role of PARP‐1 during Dictyostelium discoideum development by its constitutive downregulation as well as by PARP‐1 ortholog, ADP ribosyl transferase 1 A (ADPRT1A) overexpression. The current study analyses and strengthens the function of ADPRT1A in multicellular morphogenesis of D. discoideum. ADPRT1A was knocked out, and its effect was studied on cAMP signalling, chemotaxis and development of D. discoideum. Results We report that ADPRT1A is essential in multicellular development of D. discoideum, particularly at the aggregation stage. Genetic alterations of ADPRT1A and chemical inhibition of its activity affects the intracellular and extracellular cAMP levels during aggregation along with chemotaxis. Exogenous cAMP pulses could rescue this defect in the ADPRT1A knockout (ADPRT1A KO). Expression analysis of genes involved in cAMP signalling reveals altered transcript levels of four essential genes (PDSA, REGA, ACAA and CARA). Moreover, ADPRT1A KO affects prespore‐ and prestalk‐specific gene expression and prestalk tendency is favoured in the ADPRT1A KO. Conclusion ADPRT1A plays a definite role in regulating developmental morphogenesis via cAMP signalling. Significance This study helps in understanding the role of PARP‐1 in multicellular development and differentiation in higher complex organisms.

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Regulation of aggregate size and pattern by adenosine and caffeine in cellular slime molds

Cited by 16 publications

References 59 publications

Autophagy inDictyostelium: Mechanisms, regulation and disease in a simple biomedical model

Autophagy inDictyostelium: Mechanisms, regulation and disease in a simple biomedical model

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

Poly(ADP‐ribose) polymerase‐1 (PARP‐1) regulates developmental morphogenesis and chemotaxis in Dictyostelium discoideum

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