Cyclic AMP gradient in migrating pseudoplasmodia of the cellular slime mold Dictyostelium discoideum.

Brenner, Michael P.

doi:10.1016/s0021-9258(17)40234-1

Cited by 66 publications

(1 citation statement)

References 22 publications

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“…In the 24-h asexual life cycle of D. discoideum , a starved population of amoebae aggregate to form complex multicellular structures in a time-dependent manner ( Fey et al, 2007 ; Gaudet et al, 2008 ; Mathavarajah et al, 2017 ; Figure 3A ). After aggregating to form a mound, cells rise above the surface to form a finger, which then falls on the surface to form a motile pseudoplasmodium, or slug ( Raper, 1940 ; Brenner, 1977 ). As multicellular development continues, the slug forms a culminant where cells undergo terminal differentiation to form a fruiting body, the final stage of development ( Marée and Hogeweg, 2001 ).…”

Section: The Life Cycle Of Dictyostelium Discoideummentioning

confidence: 99%

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

2022

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“Cullins (CULs) are a core components” of cullin-RING E3 ubiquitin ligases (CRLs), which regulate the degradation, function, and subcellular trafficking of proteins. CULs 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 owing to 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.

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Section: The Life Cycle Of Dictyostelium Discoideummentioning

confidence: 99%

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

2022

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Cyclic AMP‐dependent protein kinase A plays a role in the directed migration of human keratinocytes in a DC electric field

Pullar

Isseroff

Nuccitelli

2001

Cell Motil. Cytoskeleton

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Skin wound healing requires epithelial cell migration for re-epithelialization, wound closure, and re-establishment of normal function. We believe that one of the earliest signals to initiate wound healing is the lateral electric field generated by the wound current. Normal human epidermal keratinocytes migrate towards the negative pole, representing the center of the wound, in direct currents of a physiological strength, 100 mV/mm. Virtually nothing is known about the signal transduction mechanisms used by these cells to sense the endogenous electric field. To elucidate possible protein kinase (PK) involvement in the process, PK inhibitors were utilized. Two important findings have been described. Firstly, addition of 50 nM KT5720, an inhibitor of PKA, resulted in a 53% percent reduction in the directional response of keratinocytes in the electric field, while not significantly affecting general cell motility. The reduction was dose-dependent, there was a gradual decrease in the directional response from 5 to 50 nM. Secondly, addition of 1 microM ML-7, a myosin light chain kinase inhibitor, resulted in an approximate 31% decrease in the distance the cells migrated without affecting directional migration. The PKC inhibitors GF109203X at 4 microM and H-7 at 20 microM and W-7, a CaM kinase inhibitor, did not significantly alter either directed migration or cell migration, although they all resulted in a slight reduction in directional migration. D-erythro-sphingosine at 15 microM, a PKC inhibitor, had virtually no effect on either migration distance or directed migration. These findings demonstrate that divergent kinase signaling pathways regulate general cell motility and sustained directional migration and highlight the complexity of the signal transduction mechanisms involved. The inhibitor studies described in this paper implicate a role for PKA in the regulation of the directional migratory response to applied electric fields, galvanotaxis.

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Measurements of metabolites during cAMP oscillations of Dictyostelium discoideum

Geller

Brenner

1978

Journal Cellular Physiology

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During aggregation the cellular slime mold Dictyostelium discoideum synthesizes and releases pulses of cAMP about every five minutes. Current models proposed to explain this phenomenon postulate that oscillating levels of some key intracellular metabolite control the oscillatory synthesis of cAMP. We have assayed the levels of likely candidates for this metabolite during a cAMP oscillation, but have found them to remain constant. Compounds measured include ATP, GTP, glucose-1-phosphate, glucose-6-phosphate, isocitrate, alpha-ketoglutarate, amino acids, and other aminated metabolites. On the basis of this negative data, as well as results described elsewhere (Geller and Brenner, '78), we question whether the proposed models are correct, and discuss several alternatives.

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Cyclic AMP gradient in migrating pseudoplasmodia of the cellular slime mold Dictyostelium discoideum.

Cited by 66 publications

References 22 publications

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

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

Cyclic AMP‐dependent protein kinase A plays a role in the directed migration of human keratinocytes in a DC electric field

Measurements of metabolites during cAMP oscillations of Dictyostelium discoideum

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