Acute downregulation of emerin alters actomyosin cytoskeleton connectivity and function

Qianru Jin; Deepesh Pandey; Carol B Thompson; Shawna Lewis; Hyun Woo Sung; Thao D Nguyen; Scot Kuo; Katherine L Wilson; David H Gracias; Lewis H Romer

doi:10.1016/j.bpj.2023.05.027

Acute downregulation of emerin alters actomyosin cytoskeleton connectivity and function

Biophys J. 2023 Sep 19;122(18):3690-3703. doi: 10.1016/j.bpj.2023.05.027. Epub 2023 May 29.

Authors

Affiliations

¹ Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland.
² Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland.
³ Biostatistics Center, Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
⁴ Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland.
⁵ Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Cell Biology, Johns Hopkins School of Medicine, Baltimore, Maryland; Microscope Facility, Johns Hopkins School of Medicine, Baltimore, Maryland.
⁶ Department of Cell Biology, Johns Hopkins School of Medicine, Baltimore, Maryland.
⁷ Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland; Center for MicroPhysiological Systems, Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland; Department of Chemistry, Johns Hopkins University, Baltimore, Maryland; Laboratory for Computational Sensing and Robotics, Johns Hopkins University, Baltimore, Maryland.
⁸ Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Cell Biology, Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland; Center for Cell Dynamics, Johns Hopkins School of Medicine, Baltimore, Maryland. Electronic address: lromer@jhmi.edu.

PMID: 37254483
PMCID: PMC10541481 (available on 2024-09-19)
DOI: 10.1016/j.bpj.2023.05.027

Abstract

Fetal lung fibroblasts contribute dynamic infrastructure for the developing lung. These cells undergo dynamic mechanical transitions, including cyclic stretch and spreading, which are integral to lung growth in utero. We investigated the role of the nuclear envelope protein emerin in cellular responses to these dynamic mechanical transitions. In contrast to control cells, which briskly realigned their nuclei, actin cytoskeleton, and extracellular matrices in response to cyclic stretch, fibroblasts that were acutely downregulated for emerin showed incomplete reorientation of both nuclei and actin cytoskeleton. Emerin-downregulated fibroblasts were also aberrantly circular in contrast to the spindle-shaped controls and exhibited an altered pattern of filamentous actin organization that was disconnected from the nucleus. Emerin knockdown was also associated with reduced myosin light chain phosphorylation during cell spreading. Interestingly, emerin-downregulated fibroblasts also demonstrated reduced fibronectin fibrillogenesis and production. These findings indicate that nuclear-cytoskeletal coupling serves a role in the dynamic regulation of cytoskeletal structure and function and may also impact the transmission of traction force to the extracellular matrix microenvironment.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Actin Cytoskeleton / metabolism
Actomyosin* / metabolism
Cytoskeleton* / metabolism
Down-Regulation

Substances

emerin
Actomyosin

Grants and funding

UL1 TR001079/TR/NCATS NIH HHS/United States