Nesprin-3 regulates endothelial cell morphology, perinuclear cytoskeletal architecture, and flow-induced polarization

Joshua T. Morgan, Emily R. Pfeiffer, Twanda L. Thirkill, Priyadarsini Kumar, Gordon Peng, Heidi N. Fridolfsson, Gordon C Douglas, Daniel A. Starr, Abdul I. Barakat

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Changes in blood flow regulate gene expression and protein synthesis in vascular endothelial cells, and this regulation is involved in the development of atherosclerosis. How mechanical stimuli are transmitted from the endothelial luminal surface to the nucleus is incompletely understood. The linker of nucleus and cytoskeleton (LINC) complexes have been proposed as part of a continuous physical link between the plasma membrane and subnuclear structures. LINC proteins nesprin-1, -2, and -4 have been shown to mediate nuclear positioning via microtubule motors and actin. Although nesprin-3 connects intermediate filaments to the nucleus, no functional consequences of nesprin-3 mutations on cellular processes have been described. Here we show that nesprin-3 is robustly expressed in human aortic endothelial cells (HAECs) and localizes to the nuclear envelope. Nesprin-3 regulates HAEC morphology, with nesprin-3 knockdown inducing prominent cellular elongation. Nesprin-3 also organizes perinuclear cytoskeletal organization and is required to attach the centrosome to the nuclear envelope. Finally, nesprin-3 is required for flow-induced polarization of the centrosome and flow-induced migration in HAECs. These results represent the most complete description to date of nesprin-3 function and suggest that nesprin-3 regulates vascular endothelial cell shape, perinuclear cytoskeletal architecture, and important aspects of flow-mediated mechanotransduction.

Original languageEnglish (US)
Pages (from-to)4324-4334
Number of pages11
JournalMolecular Biology of the Cell
Volume22
Issue number22
DOIs
StatePublished - Nov 15 2011

Fingerprint

Endothelial Cells
Centrosome
Nuclear Envelope
Cytoskeleton
Intermediate Filaments
Cell Shape
Microtubules
Actins
Atherosclerosis
Proteins
Cell Membrane
Gene Expression
Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Morgan, J. T., Pfeiffer, E. R., Thirkill, T. L., Kumar, P., Peng, G., Fridolfsson, H. N., ... Barakat, A. I. (2011). Nesprin-3 regulates endothelial cell morphology, perinuclear cytoskeletal architecture, and flow-induced polarization. Molecular Biology of the Cell, 22(22), 4324-4334. https://doi.org/10.1091/mbc.E11-04-0287

Nesprin-3 regulates endothelial cell morphology, perinuclear cytoskeletal architecture, and flow-induced polarization. / Morgan, Joshua T.; Pfeiffer, Emily R.; Thirkill, Twanda L.; Kumar, Priyadarsini; Peng, Gordon; Fridolfsson, Heidi N.; Douglas, Gordon C; Starr, Daniel A.; Barakat, Abdul I.

In: Molecular Biology of the Cell, Vol. 22, No. 22, 15.11.2011, p. 4324-4334.

Research output: Contribution to journalArticle

Morgan, JT, Pfeiffer, ER, Thirkill, TL, Kumar, P, Peng, G, Fridolfsson, HN, Douglas, GC, Starr, DA & Barakat, AI 2011, 'Nesprin-3 regulates endothelial cell morphology, perinuclear cytoskeletal architecture, and flow-induced polarization', Molecular Biology of the Cell, vol. 22, no. 22, pp. 4324-4334. https://doi.org/10.1091/mbc.E11-04-0287
Morgan, Joshua T. ; Pfeiffer, Emily R. ; Thirkill, Twanda L. ; Kumar, Priyadarsini ; Peng, Gordon ; Fridolfsson, Heidi N. ; Douglas, Gordon C ; Starr, Daniel A. ; Barakat, Abdul I. / Nesprin-3 regulates endothelial cell morphology, perinuclear cytoskeletal architecture, and flow-induced polarization. In: Molecular Biology of the Cell. 2011 ; Vol. 22, No. 22. pp. 4324-4334.
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