Nuclear SUN2 coordinates endothelial cell-matrix interactions to regulate blood vessel homeostasis and barrier function.
12 affiliations
- 1Department of Biology, The University of North Carolina at Chapel Hill, CB No, 3280, Chapel Hill, NC, 27599, USA.
- 2Curriculum in Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- 3Department of Biomedical Engineering, Lampe Joint, , University of North Carolina Chapel Hill and North Carolina State University, North Carolina, USA.
- 4Department of Pharmacology, University of North Carolina-Chapel Hill Medical School, Chapel Hill, NC, USA.
- 5Department of Physiology and Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
- 6Department of Cell Biology and Physiology, UNC-Chapel Hill School of Medicine, Chapel Hill, NC, USA.
- 7UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.
- 8McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- 9Department of Biology, The University of North Carolina at Chapel Hill, CB No, 3280, Chapel Hill, NC, 27599, USA. [email protected].
- 10Curriculum in Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. [email protected].
- 11UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA. [email protected].
- 12McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. [email protected].
Abstract
Vascular endothelial cells respond to environmental forces to remodel vessels during development and to achieve homeostasis, and mis-regulated responses lead to vascular dysfunction and disease. The nucleus participates in transmitting signals to cell-matrix junctions via the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex that resides in the nuclear envelope, but how this information is regulated and relayed is incompletely understood. We found that the LINC complex protein SUN2 is required for proper endothelial cell-matrix interactions that occur far from the nucleus and affect angiogenic expansion, vascular responses to flow, and barrier integrity. Endothelial cells lacking SUN2 had inappropriate responses to environmental cues generated under both non-flow and flow conditions as well as reduced expression of flow-mediated transcription factors in vitro and in vivo. Expression of several matrix and adhesion genes was reduced in SUN2-depleted cells and associated with defective extracellular matrix, dysmorphic focal adhesions resistant to dynamic turnover, and disturbed cell-matrix force distribution. Mechanistically, nuclear SUN2 regulated cytoskeletal microtubule dynamics upstream of effects on cell and focal adhesion morphology, barrier integrity, and flow-mediated endothelial quiescence. These findings indicate that nuclear SUN2 establishes and maintains blood vessel homeostasis by controlling microtubule-mediated effects on focal adhesion and extracellular matrix properties, with implications for cardiovascular aging and diseases such as Marfan syndrome that affect vessel wall integrity.
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BibTeX
@article{bougaran2026nuclear,
title = {{Nuclear SUN2 coordinates endothelial cell-matrix interactions to regulate blood vessel homeostasis and barrier function.}},
author = {Pauline Bougaran and Danielle B Buglak and Alexandra Neal and Mitesh Rathod and Michaelanthony Gore and Max A Hockenberry and Aryan A Amin and Natalie Tanke and Morgan Oatley and Wesley R Legant and Ziqing Liu and James E Bear and William J Polacheck and Victoria L Bautch},
journal = {Angiogenesis},
year = {2026},
month = oct,
doi = {10.1007/s10456-026-10098-w},
url = {https://europepmc.org/article/MED/42878933},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Nuclear SUN2 coordinates endothelial cell-matrix interactions to regulate blood vessel homeostasis and barrier function.
AU - Pauline Bougaran
AU - Danielle B Buglak
AU - Alexandra Neal
AU - Mitesh Rathod
AU - Michaelanthony Gore
AU - Max A Hockenberry
AU - Aryan A Amin
AU - Natalie Tanke
AU - Morgan Oatley
AU - Wesley R Legant
AU - Ziqing Liu
AU - James E Bear
AU - William J Polacheck
AU - Victoria L Bautch
PY - 2026
DA - 2026/10/15
JO - Angiogenesis
DO - 10.1007/s10456-026-10098-w
UR - https://europepmc.org/article/MED/42878933
AB - Vascular endothelial cells respond to environmental forces to remodel vessels during development and to achieve homeostasis, and mis-regulated responses lead to vascular dysfunction and disease. The nucleus participates in transmitting signals to cell-matrix junctions via the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex that resides in the nuclear envelope, but how this information is regulated and relayed is incompletely understood. We found that the LINC complex protein SUN2 is required for proper endothelial cell-matrix interactions that occur far from the nucleus and affect angiogenic expansion, vascular responses to flow, and barrier integrity. Endothelial cells lacking SUN2 had inappropriate responses to environmental cues generated under both non-flow and flow conditions as well as reduced expression of flow-mediated transcription factors in vitro and in vivo. Expression of several matrix and adhesion genes was reduced in SUN2-depleted cells and associated with defective extracellular matrix, dysmorphic focal adhesions resistant to dynamic turnover, and disturbed cell-matrix force distribution. Mechanistically, nuclear SUN2 regulated cytoskeletal microtubule dynamics upstream of effects on cell and focal adhesion morphology, barrier integrity, and flow-mediated endothelial quiescence. These findings indicate that nuclear SUN2 establishes and maintains blood vessel homeostasis by controlling microtubule-mediated effects on focal adhesion and extracellular matrix properties, with implications for cardiovascular aging and diseases such as Marfan syndrome that affect vessel wall integrity.
SN - 0969-6970
SN - 1573-7209
ER -