Nesprin-3, a protein that links intermediate filaments to the nucleus, plays a role in vascular endothelial cell (EC) function. Nesprin-3 regulates EC morphology, perinuclear cytoskeletal organization, centrosome–nuclear connectivity, and flow-induced cell polarization and migration

Abdul I. Barakat

Ando J

Andra K

Apel ED

Brosig M

Cao Y

Chancellor TJ

Chen CS

Chien S

Crisp M

Dahl KN

Daniel A. Starr

Davies PF

Emily R. Pfeiffer

Galbraith CG

Gieni RS

Gojova A

Gomes ER

Gordon C. Douglas

Gordon Peng

Grady RM

Gray BL

Gros-Louis F

Heidi N. Fridolfsson

Henrion D

Hu S

Huveneers S

Hynes RO

Joshua T. Morgan

Ketema M

Lee JS

Liliensiek SJ

Malech HL

Maniotis AJ

Masuda M

Mazzag BM

McCue S

Na S

Neumann S

Niwa T

Padmakumar VC

Postel R

Priyadarsini Kumar

Puckelwartz MJ

Razafsky D

Robert David Goldman

Rogers KA

Roux KJ

Salpingidou G

Schneider M

Starr DA

Stewart-Hutchinson PJ

Suvatne J

Twanda L. Thirkill

Tzima E

Vartanian KB

Wang N

Westwood SM

Wheeler MA

Wilhelmsen K

Zhang J

Zhang Q

Zhang X

Zhen YY

PubMed

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.</jats:p

Crossref

Molecular Biology of the Cell

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

International audienceChanges 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. © 2011 Morgan et al

Morgan, J.T.

Pfeiffer, E.R.

Thirkill, T.L.

Kumar, P.

Peng, G.

Fridolfsson, H.N.

Douglas, G.C.

Starr, D.A.

Barakat, Abdul, I.

HAL: Hyper Article en Ligne

HAL-Polytechnique

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 morpho-logy, 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

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

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HAL-Polytechnique

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