SUN1/2 controls macrophage polarization via modulating nuclear size and stiffness

Shi Jiao (), Chuanchuan Li, Fenghua Guo, Jinjin Zhang, Hui Zhang, Zhifa Cao, Wenjia Wang, Wenbo Bu, Mobin Lin (), Junhong Lü () and Zhaocai Zhou ()
Additional contact information
Shi Jiao: Fudan University
Chuanchuan Li: University of Chinese Academy of Sciences
Fenghua Guo: Fudan University Shanghai Medical College
Jinjin Zhang: Chinese Academy of Sciences
Hui Zhang: Fudan University
Zhifa Cao: Tongji University School of Medicine
Wenjia Wang: Fudan University
Wenbo Bu: Fudan University
Mobin Lin: Tongji University School of Medicine
Junhong Lü: Chinese Academy of Sciences
Zhaocai Zhou: Fudan University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Alteration of the size and stiffness of the nucleus triggered by environmental cues are thought to be important for eukaryotic cell fate and function. However, it remains unclear how context-dependent nuclear remodeling occurs and reprograms gene expression. Here we identify the nuclear envelope proteins SUN1/2 as mechano-regulators of the nucleus during M1 polarization of the macrophage. Specifically, we show that LPS treatment decreases the protein levels of SUN1/2 in a CK2-βTrCP-dependent manner to shrink and soften the nucleus, therefore altering the chromatin accessibility for M1-associated gene expression. Notably, the transmembrane helix of SUN1/2 is solely required and sufficient for the nuclear mechano-remodeling. Consistently, SUN1/2 depletion in macrophages facilitates their phagocytosis, tissue infiltration, and proinflammatory cytokine production, thereby boosting the antitumor immunity in mice. Thus, our study demonstrates that, in response to inflammatory cues, SUN1/2 proteins act as mechano-regulators to remodel the nucleus and chromatin for M1 polarization of the macrophage.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-42187-5 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:14:y:2023:i:1:d:10.1038_s41467-023-42187-5

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

DOI: 10.1038/s41467-023-42187-5

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 ().