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

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

doi:10.1091/mbc.e11-04-0287

Cited by 102 publications

(100 citation statements)

References 63 publications

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“…Vascular endothelial cells are known to alter their shape in response to diverse factors such as mechanical and biochemical stimuli, which influence a variety of cellular functions (47). In this study, we observed that knockdown of TRPM7 dramatically alters the morphology of HUVECs: they change from flat and rounded shape to constricted and elongated morphology.…”

Section: Discussionmentioning

confidence: 64%

“…As a change in cell shape directly affects cell function including proliferation, apoptosis, and inflammation in various cell types (8,9,47,70), the change in the morphology of HUVECs induced by knockdown of TRPM7 suggests that TRPM7 may play an important role in regulating the functions of endothelium under physiological and pathological conditions. Our data suggest that a reduced level of TRPM7 might facilitate the vascular repair in case of damage through enhanced angiogenic activity.…”

Section: Discussionmentioning

confidence: 99%

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TRPM7 regulates vascular endothelial cell adhesion and tube formation

Zeng

Inoue

Sun

et al. 2015

American Journal of Physiology-Cell Physiology

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sient receptor potential melastatin 7 (TRPM7) is a nonselective cation channel with an ␣-kinase domain in its COOH terminal, known to play a role in diverse physiological and pathological processes such as Mg 2ϩ homeostasis, cell proliferation, and hypoxic neuronal injury. Increasing evidence suggests that TRPM7 contributes to the physiology/pathology of vascular systems. For example, we recently demonstrated that silencing TRPM7 promotes growth and proliferation and protects against hyperglycemia-induced injury in human umbilical vein endothelial cells (HUVECs). Here we investigated the potential effects of TRPM7 on morphology, adhesion, migration, and tube formation of vascular endothelial cells and the potential underlying mechanism. We showed that inhibition of TRPM7 function in HUVECs by silencing TRPM7 decreases the density of TRPM7-like current and cell surface area and inhibits cell adhesion to Matrigel. Silencing TRPM7 also promotes cell migration, wound healing, and tube formation. Further studies showed that the extracellular signalregulated kinase (ERK) pathway is involved in the change of cell morphology and the increase in HUVEC migration induced by TRPM7 silencing. We also demonstrated that silencing TRPM7 enhances the phosphorylation of myosin light chain (MLC) in HUVECs, which might be involved in the enhancement of cell contractility and motility. Collectively, our data suggest that the TRPM7 channel negatively regulates the function of vascular endothelial cells. Further studies on the underlying mechanism may facilitate the development of the TRPM7 channel as a target for the therapeutic intervention of vascular diseases.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

TRPM7 regulates vascular endothelial cell adhesion and tube formation

Zeng

Inoue

Sun

et al. 2015

American Journal of Physiology-Cell Physiology

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“…Developmental differences in anchoring to the microtubule cytoskeleton can also be seen in this organism: in embryos, the KASH protein ZYG-12 is required for localization of dynein and centrosome tethering via SUN-1, but in epidermal hypodermal precursor cells the KASH protein UNC-83 and the SUN protein UNC-84 are important for microtubule tethering in a centrosome-independent pathway [56,71]. In cultured mammalian neurons, glial cells or kerotinocytes, Sun1/2 and the KASH proteins Syne/Nesprin-1/2 make the connection between the centrosome and the nucleus, while centrosome tethering in human aortic endothelial cells is dependent on nesprin-3 and intermediate filaments [58,69,[72][73][74]. However, studies in HeLa cells reveal a dependence on nucleoporins for centrosome tethering at the NE while reports from human and murine fibroblast investigations have shown the INM protein emerin mediates the centrosome-NE attachment through an interaction with tubulin [69 ,75,76].…”

Section: Centrosomes and Nuclear Envelope Breakdownmentioning

confidence: 99%

Breaking down the wall: the nuclear envelope during mitosis

Smoyer

Jaspersen

2014

Current Opinion in Cell Biology

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A defining feature of eukaryotic cells is the nucleus, which houses the genome inside the nuclear envelope (NE): a double lipid bilayer that separates the nuclear and cytoplasmic materials. Although the NE is commonly viewed as a barrier that is overcome only by embedded nuclear pore complexes (NPCs) that facilitate nuclear-cytoplasmic trafficking, recent work in a wide range of eukaryotes reveals that the NE is a dynamic organelle that is modified each time the cell divides to ultimately establish two functional daughter nuclei. Here, we review how studies of divergent mitotic strategies have helped elucidate common properties of NE biology that allow it to function throughout the cell cycle.

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“…Through the plectin-binding domain, Nesprin-3 can connect the NE to the intermediate fi lament system [ 7 ]. Nesprin-3 defi ciency leads to reduced amounts of perinuclear intermediate fi laments as shown in zebrafi sh [ 8 ] or human aortic endothelial cells [ 9 ]. Finally, Nesprin-2 and -4 interact with the microtubule network through interactions with the microtubule motor protein Kinesin-1 [ 10 , 11 ].…”

Section: Nesprinsmentioning

confidence: 99%

Nesprins in Cell Stability and Migration

Neumann

Noegel

2014

Cancer Biology and the Nuclear Envelope

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Nesprins are a family of proteins that are primarily known for their localization along the nuclear envelope. Together with inner nuclear membrane SUN proteins, they form the core of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex that traverses both nuclear membranes to connect the cytoplasm and the nuclear interior. Based on their structure and interactions, Nesprins integrate the nucleus into the cytoskeleton of a cell. Mutations in Nesprins have been identified in a group of human diseases that have been summarized as laminopathies. Cellular functions of the Nesprins and recent studies on different cancer types additionally draw interest on Nesprins in the field of cancer research. Here we summarize recent findings about the structural arrangements of Nesprins along the nuclear envelope, and highlight Nesprin functions in basic cellular processes like maintenance of nuclear shape and size, and of nuclear and cellular or cytoskeletal organization, centrosomal positioning, cell migration, and signal transduction. In summary, Nesprins are involved in critical cellular processes, which in case of malfunction contribute to the formation of cancer and might represent novel targets in cancer diagnosis or for therapeutic intervention.

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

Abstract: 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.

Cited by 102 publications

References 63 publications

TRPM7 regulates vascular endothelial cell adhesion and tube formation

TRPM7 regulates vascular endothelial cell adhesion and tube formation

Breaking down the wall: the nuclear envelope during mitosis

Nesprins in Cell Stability and Migration

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