Faculty Collaboration Database

Nuclear SUN1 stabilizes endothelial cell junctions via microtubules to regulate blood vessel formation. Elife 2023 Mar 29;12

Date

03/30/2023

Pubmed ID

36989130

Pubmed Central ID

PMC10059686

DOI

10.7554/eLife.83652

Scopus ID

2-s2.0-85151312541 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

Endothelial cells line all blood vessels, where they coordinate blood vessel formation and the blood-tissue barrier via regulation of cell-cell junctions. The nucleus also regulates endothelial cell behaviors, but it is unclear how the nucleus contributes to endothelial cell activities at the cell periphery. Here, we show that the nuclear-localized linker of the nucleoskeleton and cytoskeleton (LINC) complex protein SUN1 regulates vascular sprouting and endothelial cell-cell junction morphology and function. Loss of murine endothelial Sun1 impaired blood vessel formation and destabilized junctions, angiogenic sprouts formed but retracted in SUN1-depleted sprouts, and zebrafish vessels lacking Sun1b had aberrant junctions and defective cell-cell connections. At the cellular level, SUN1 stabilized endothelial cell-cell junctions, promoted junction function, and regulated contractility. Mechanistically, SUN1 depletion altered cell behaviors via the cytoskeleton without changing transcriptional profiles. Reduced peripheral microtubule density, fewer junction contacts, and increased catastrophes accompanied SUN1 loss, and microtubule depolymerization phenocopied effects on junctions. Depletion of GEF-H1, a microtubule-regulated Rho activator, or the LINC complex protein nesprin-1 rescued defective junctions of SUN1-depleted endothelial cells. Thus, endothelial SUN1 regulates peripheral cell-cell junctions from the nucleus via LINC complex-based microtubule interactions that affect peripheral microtubule dynamics and Rho-regulated contractility, and this long-range regulation is important for proper blood vessel sprouting and junction integrity.

Author List

Buglak DB, Bougaran P, Kulikauskas MR, Liu Z, Monaghan-Benson E, Gold AL, Marvin AP, Burciu A, Tanke NT, Oatley M, Ricketts SN, Kinghorn K, Johnson BN, Shiau CE, Rogers S, Guilluy C, Bautch VL

Author

Ziqing Liu PhD Assistant Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Endothelial Cells
Intercellular Junctions
Mice
Microtubule-Associated Proteins
Microtubules
Nuclear Proteins
Zebrafish