MARK4 regulates NLRP3 positioning and inflammasome activation through a microtubule-dependent mechanism

Xuan Li (), Sarah Thome, Xiaodan Ma, Mamta Amrute-Nayak, Alison Finigan, Lauren Kitt, Leanne Masters, John R. James, Yuguang Shi, Guoyu Meng and Ziad Mallat ()
Additional contact information
Xuan Li: University of Cambridge
Sarah Thome: University of Cambridge
Xiaodan Ma: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui-Jin Hospital affiliated to Shanghai JiaoTong University School of Medicine
Mamta Amrute-Nayak: Hannover Medical School
Alison Finigan: University of Cambridge
Lauren Kitt: University of Cambridge
Leanne Masters: University of Cambridge
John R. James: Molecular Immunity Unit, University of Cambridge, MRC-LMB
Yuguang Shi: Barshop Institute for longevity and Aging Studies, University of Texas Health Science Center at San Antonio. Texas Research Park Campus MC 7755
Guoyu Meng: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui-Jin Hospital affiliated to Shanghai JiaoTong University School of Medicine
Ziad Mallat: University of Cambridge

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract Excessive activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome is involved in many chronic inflammatory diseases, including cardiovascular and Alzheimer’s disease. Here we show that microtubule-affinity regulating kinase 4 (MARK4) binds to NLRP3 and drives it to the microtubule-organizing centre, enabling the formation of one large inflammasome speck complex within a single cell. MARK4 knockdown or knockout, or disruption of MARK4-NLRP3 interaction, impairs NLRP3 spatial arrangement and limits inflammasome activation. Our results demonstrate how an evolutionarily conserved protein involved in the regulation of microtubule dynamics orchestrates NLRP3 inflammasome activation by controlling its transport to optimal activation sites, and identify a targetable function for MARK4 in the control of innate immunity.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms15986 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15986

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms15986

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().