The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.
Protein kinase D at the Golgi controls NLRP3 inflammasome activation
Open accessAbstract
The inflammasomes are multiprotein complexes sensing tissue damage and infectious agents to initiate innate immune responses. Different inflammasomes containing distinct sensor molecules exist. The NLRP3 inflammasome is unique as it detects a variety of danger signals. It has been reported that NLRP3 is recruited to mitochondria-associated endoplasmic reticulum membranes (MAMs) and is activated by MAM-derived effectors. Here, we show that in response to inflammasome activators, MAMs localize adjacent to Golgi membranes. Diacylglycerol (DAG) at the Golgi rapidly increases, recruiting protein kinase D (PKD), a key effector of DAG. Upon PKD inactivation, self-oligomerized NLRP3 is retained at MAMs adjacent to Golgi, blocking assembly of the active inflammasome. Importantly, phosphorylation of NLRP3 by PKD at the Golgi is sufficient to release NLRP3 from MAMs, resulting in assembly of the active inflammasome. Moreover, PKD inhibition prevents inflammasome autoactivation in peripheral blood mononuclear cells from patients carrying NLRP3 mutations. Hence, Golgi-mediated PKD signaling is required and sufficient for NLRP3 inflammasome activation.
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The role of mitochondria in NLRP3 inflammasome activation
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Metadata
- Authors
- Zhang, Z., Meszaros, G., He, W.-T., Xu, Y., de Fatima Magliarelli, H., Mailly, L., Mihlan, M., Liu, Y., Puig Gámez, M., Goginashvili, A., Pasquier, A., Bielska, O., Neven, B., Quartier, P., Aebersold, R., Baumert, T. F., Georgel, P., Han, J., & Ricci, R.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2017-07-17
- Volume
- 214
- Issue
- 9
- Pages
- 2671-2693
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2735208690
- Cited by
- 282
- References
- 74
- FWCI
- 7.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Zhang, Z., Meszaros, G., He, W.-T., Xu, Y., de Fatima Magliarelli, H., Mailly, L., Mihlan, M., Liu, Y., Puig Gámez, M., Goginashvili, A., Pasquier, A., Bielska, O., Neven, B., Quartier, P., Aebersold, R., Baumert, T. F., Georgel, P., Han, J., & Ricci, R. (2017). Protein kinase D at the Golgi controls NLRP3 inflammasome activation. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20162040
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