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Reposted by Elvira Boršić Mlinarič

CTGCT (Centre for the Technologies of Gene and Cell Therapy) @ctgct.bsky.social · 25/09/2025

#CTGCT Science Talks are back! This time we have a talk open to everyone by dr. Iva Hafner Bratkovič from the Department of Synthetic Biology and Immunology at the @kemijski.bsky.social. Her talk is titled "Inflammasome-inspired cancer immunotherapy" Join us! forms.office.com/e/KJTTsMyETk #Webinar

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Reposted by Elvira Boršić Mlinarič

Jonathan Kagan @jkagan1.bsky.social · 27/05/2025

NLRP3 inflammasomes can assemble on most organelles. A beautiful study by Hafner et al demonstrate the flexibility of organelles that can support inflammasome activation. Kudos to the authors on an intriguing study. www.nature.com/articles/s41... @ivahb.bsky.social @elvirab.bsky.social

nature.com

Clustering of NLRP3 induced by membrane or protein scaffolds promotes inflammasome assembly - Nature Communications

NLRP3 inflammasome activation is critical for the induction of protective immunity, but molecular insights are still lacking. Here, the authors express NLRP3 variants targeted to different cellular lo...

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Elvira Boršić Mlinarič @elvirab.bsky.social · 27/05/2025

Huge thanks to our incredible team of Pyrocellfluencers @kemijski.bsky.social and collaborators: Taja Železnik Ramuta, Sara Orehek, Mateja Erdani Kreft, Matthias Geyer, Roman Jerala and @ivahb.bsky.social. 🔥💪

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Elvira Boršić Mlinarič @elvirab.bsky.social · 27/05/2025

Subcellular location of NLRP3 is not essential, but clustering on different scaffolds is. This explains how NLRP3 can react to so many diverse stress signals. 9/9

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Elvira Boršić Mlinarič @elvirab.bsky.social · 27/05/2025

Surprisingly, this activation could not be blocked by MCC950, suggesting that clustering of NLRP3 induces rearrangements of inactive NLRP3 leading to active NACHT-based oligomer formation. 8/9

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Elvira Boršić Mlinarič @elvirab.bsky.social · 27/05/2025

To test if lipid membranes are truly dispensable, we fused NLRP3 to TDP43, a protein that forms cytosolic condensates. That alone was enough to trigger inflammasome assembly without any external stimulus. 7/9

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Elvira Boršić Mlinarič @elvirab.bsky.social · 27/05/2025

We showed that NLRP3 can be activated from different types of scaffolds not just membranes. Variants targeted to the Golgi (GOLGB1) or centrosome (PACT) triggered IL-1β release after priming alone. Both formed multiple spots in the cell, resembling activated NLRP3. 6/9

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Elvira Boršić Mlinarič @elvirab.bsky.social · 27/05/2025

The polybasic segment in NLRP3 is highly conserved and known to mediate lipid binding. We mutated this region (4xA) to test if it is essential for activation. Interestingly, membrane-enriched variants still triggered IL-1β secretion, whereas cytosolic 4xA failed. 5/9

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Elvira Boršić Mlinarič @elvirab.bsky.social · 27/05/2025

All designed variants formed a functional inflammasome judged by ASC speck formation and their activation was K+ efflux-dependent. 4/9

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Elvira Boršić Mlinarič @elvirab.bsky.social · 27/05/2025

We engineered NLRP3 to localize to different organelles: ER, Golgi, plasma membrane, lysosomes, mitochondria and peroxisomes. Surprisingly, all location-restricted variants supported IL-1β release when stimulated with different activators. 3/9

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Elvira Boršić Mlinarič @elvirab.bsky.social · 27/05/2025

It is enigmatic how NLRP3 can be triggered by many different and unrelated signals. We wanted to know whether the subcellular location of NLRP3 plays a role. 2/9

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Reposted by Elvira Boršić Mlinarič

Waggoner Lab @labwaggoner.bsky.social · 10/02/2025

Mechanisms of NLRP3 activation and inhibition elucidated by functional analysis of disease-associated variants www.nature.com/articles/s41... @natimmunol.bsky.social @sethlucianmasters.bsky.social

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