ATP as a biological hydrotrope

Patel, Avinash; Malinovska, Liliana; Saha, Shambaditya; Wang, Jie; Alberti, Simon; Krishnan, Yamuna; Hyman, Anthony

doi:10.1126/science.aaf6846

Cited by 777 publications

(924 citation statements)

References 38 publications

(41 reference statements)

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“…4A). The lack of effect of ATP in the latter experiment also rules out that droplet dispersion may be explained by a hydrotrope action of this nucleotide (31). Such an action, as reported for liquid droplets generated by other proteins, occurs only at much higher ATP concentration (Fig.…”

mentioning

confidence: 88%

A liquid phase of synapsin and lipid vesicles

Milovanović

Bian

et al. 2018

Science

424

419

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Neurotransmitter containing synaptic vesicles (SVs) form tight clusters at synapses. These clusters act as a reservoir from which SVs are drawn for exocytosis during sustained activity. Several components associated with synaptic vesicles likely to help forming such clusters have been reported, including synapsin. Here we found that synapsin can form a distinct liquid phase in an aqueous environment. Other scaffolding proteins could co-assemble into this condensate, but were not necessary for its formation. Importantly, the synapsin phase could capture small lipid vesicles. The synapsin phase rapidly disassembled upon phosphorylation by calcium/calmodulin-dependent protein kinase II (CaMKII), mimicking the dispersion of synapsin 1 that occurs at presynaptic sites upon stimulation. Thus, principles of liquid-liquid phase separation may apply to the clustering of SVs at synapses.

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mentioning

confidence: 88%

A liquid phase of synapsin and lipid vesicles

Milovanović

Bian

et al. 2018

Science

424

419

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“…These values are similar to previously described components of liquid-like condensates (36, 37). ATP has been implicated in promoting condensate fluidity by driving energy-dependent processes and/or through its intrinsic hydrotrope activity (38, 39). Depletion of cellular ATP by glucose deprivation and oligomycin treatment altered fluorescence recovery after photobleaching for both mEGFP-BRD4 and mEGFP-MED1 foci, with the rate of recovery for MED1 reduced and the extent of recovery for BRD4 diminished (Fig.…”

Section: Coactivator Puncta Exhibit Liquid-like Rates Of Fluorescencementioning

confidence: 99%

Coactivator condensation at super-enhancers links phase separation and gene control

Sabari

Dall’Agnese

Boija

et al. 2018

Science

1,987

111

1,868

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Super-enhancers (SEs) are clusters of enhancers that cooperatively assemble a high density of transcriptional apparatus to drive robust expression of genes with prominent roles in cell identity. Here, we demonstrate that the SE-enriched transcriptional coactivators BRD4 and MED1 form nuclear puncta at SEs that exhibit properties of liquid-like condensates and are disrupted by chemicals that perturb condensates. The intrinsically disordered regions (IDRs) of BRD4 and MED1 can form phase-separated droplets and MED1-IDR droplets can compartmentalize and concentrate transcription apparatus from nuclear extracts. These results support the idea that coactivators form phase-separated condensates at SEs that compartmentalize and concentrate the transcription apparatus, suggest a role for coactivator IDRs in this process, and offer insights into mechanisms involved in control of key cell identity genes.

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“…12 The reason why the K m value of myosin is more than 10-fold lower than the intracellular ATP concentration has remained enigmatic for a long time. The recently published paper by Patel et al 1 provides an interesting explanation for this discrepancy.…”

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confidence: 85%