Abstract
The NLRP3 inflammasome plays a central role in antimicrobial defense as well as in the context of sterile in-flammatory conditions. NLRP3 activity is governed by two independent signals: the first signal primes NLRP3, rendering it responsive to the second signal, which then triggers inflammasome formation. Our un-derstanding of how NLRP3 priming contributes to inflammasome activation remains limited. Here, we show that IKK(3, a kinase activated during priming, induces recruitment of NLRP3 to phosphatidylinositol-4-phos-phate (PI4P), a phospholipid enriched on the trans-Golgi network. NEK7, a mitotic spindle kinase that had previously been thought to be indispensable for NLRP3 activation, was redundant for inflammasome forma-tion when IKK(3 recruited NLRP3 to PI4P. Studying iPSC-derived human macrophages revealed that the IKK(3-mediated NEK7-independent pathway constitutes the predominant NLRP3 priming mechanism in hu-man myeloid cells. Our results suggest that PI4P binding represents a primed state into which NLRP3 is brought by IKK(3 activity.
| Dokumententyp: | Zeitschriftenartikel |
|---|---|
| Fakultät: | Chemie und Pharmazie > Department für Pharmazie - Zentrum für Pharmaforschung
Biologie |
| Themengebiete: | 500 Naturwissenschaften und Mathematik > 540 Chemie
500 Naturwissenschaften und Mathematik > 570 Biowissenschaften; Biologie |
| ISSN: | 1074-7613 |
| Sprache: | Englisch |
| Dokumenten ID: | 111290 |
| Datum der Veröffentlichung auf Open Access LMU: | 02. Apr. 2024, 07:24 |
| Letzte Änderungen: | 02. Apr. 2024, 07:24 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 414786233 |
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