Dataset Information

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

ABSTRACT: 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 ?-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.

SUBMITTER: Santarriaga S

PROVIDER: S-EPMC6584373 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Santarriaga Stephanie S Fikejs Alicia A Scaglione Jamie J Scaglione K Matthew KM

mSphere 20190619 3

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 ...[more]

PMID: 31217303

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Project description:DEAD-box helicases are important regulators of biomolecular condensates. However, the mechanisms through which these enzymes affect the dynamics of biomolecular condensates have not been systematically explored. Here, we demonstrate the mechanism by which mutation of a DEAD-box helicaseâ€™s catalytic core alters ribonucleoprotein condensate dynamics in the presence of ATP. Through altering RNA length within the system, we are able to attribute the altered biomolecular dynamics and material properties to physical crosslinking of RNA facilitated by the mutant helicase. These results suggest the mutant condensates approach a gel transition when RNA length is increased to lengths comparable to eukaryotic mRNA. Lastly, we show that this crosslinking effect is tunable with ATP concentration, uncovering a system whose RNA mobility and material properties vary with enzyme activity. More generally, these findings point to a fundamental mechanism for modulating condensate dynamics and emergent material properties through nonequilibrium, molecular-scale interactions.SignificanceBiomolecular condensates are membraneless organelles which organize cellular biochemistry. These structures have a diversity of material properties and dynamics which are crucial to their function. How condensate properties are determined by biomolecular interactions and enzyme activity remain open questions. DEAD-box helicases have been identified as central regulators of many protein-RNA condensates, though their specific mechanistic roles are ill-defined. In this work, we demonstrate that a DEAD-box helicase mutation crosslinks condensate RNA in an ATP-dependent fashion via protein-RNA clamping. Protein and RNA diffusion can be tuned with ATP concentration, corresponding to an order of magnitude change in condensate viscosity. These findings expand our understanding of control points for cellular biomolecular condensates that have implications for medicine and bioengineering.

Project description:BackgroundDictyostelium discoideum, a microbial model for social evolution, is known to distinguish self from non-self and show genotype-dependent behavior during chimeric development. Aside from a small number of cell-cell recognition genes, however, little is known about the genetic basis of self/non-self recognition in this species. Based on the key hypothesis that there should be differential expression of genes if D. discoideum cells were interacting with non-clone mates, we performed transcriptomic profiling study in this species during clonal vs. chimeric development. The transcriptomic profiles of D. discoideum cells in clones vs. different chimeras were compared at five different developmental stages using a customized microarray. Effects of chimerism on global transcriptional patterns associated with social interactions were observed.ResultsWe find 1,759 genes significantly different between chimera and clone, 1,144 genes associated significant strain differences, and 6,586 genes developmentally regulated over time. Principal component analysis showed a small amount of the transcriptional variance to chimerism-related factors (Chimerism: 0.18%, Chimerism × Timepoint: 0.03%). There are 162 genes specifically regulated under chimeric development, with continuous small differences between chimera vs. clone over development. Almost 60% of chimera-associated differential genes were differentially expressed at the 4 h aggregate stage, which corresponds to the initial transition of D. discoideum from solitary life to a multicellular phase.ConclusionsA relatively small proportion of over-all variation in gene expression is explained by differences between chimeric and clonal development. The relatively small modifications in gene expression associated with chimerism is compatible with the high level of cooperation observed among different strains of D. discoideum; cells of distinct genetic backgrounds will co-aggregate indiscriminately and co-develop into fruiting bodies. Chimeric development may involve re-programming of the transcriptome through small modifications of the developmental genetic network, which may also indicate that response to social interaction involves many genes with individually small transcriptional effect.

Dataset Information

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

Publications

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

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