Regulation of Vascular Endothelial Cell Polarization and Migration by Hsp70/Hsp90-Organizing Protein

Li, Jingyu; Sun, Xiaodong; Wang, Zaizhu; Chen, Li; Li, Dengwen; Zhou, Jun; Liu, Min

doi:10.1371/journal.pone.0036389

Cited by 37 publications

(24 citation statements)

References 50 publications

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“…Although HSPs were initially identified because their expression increases under conditions of high temperature and other stresses, HSPs are now known to primarily function as chaperones to facilitate protein folding and block aggregation, a potential problem associated with high levels of protein production. Alternatively, cellular stress response genes have also been shown to promote cell migration and morphogenesis (Cobreros et al, 2008; Li et al, 2012). The potential direct targets repressed by Rib in the SG, came primarily under the GO term salivary gland morphogenesis.…”

Section: Discussionmentioning

confidence: 99%

Ribbon regulates morphogenesis of the Drosophila embryonic salivary gland through transcriptional activation and repression

Loganathan

Lee

Wells

et al. 2016

Developmental Biology

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Transcription factors affect spatiotemporal patterns of gene expression often regulating multiple aspects of tissue morphogenesis, including cell-type specification, cell proliferation, cell death, cell polarity, cell shape, cell arrangement and cell migration. In this work, we describe a distinct role for Ribbon (Rib) in controlling cell shape/volume increases during elongation of the Drosophila salivary gland (SG). Notably, the morphogenetic changes in rib mutants occurred without effects on general SG cell attributes such as specification, proliferation and apoptosis. Moreover, the changes in cell shape/volume in rib mutants occurred without compromising epithelial-specific morphological attributes such as apicobasal polarity and junctional integrity. To identify the genes regulated by Rib, we performed ChIP-seq analysis in embryos driving expression of GFP-tagged Rib specifically in the SGs. To learn if the Rib binding sites identified in the ChIP-seq analysis were linked to changes in gene expression, we performed microarray analysis comparing RNA samples from age-matched wild-type and rib null embryos. From the superposed ChIP-seq and microarray gene expression data, we identified 60 genomic sites bound by Rib likely to regulate SG-specific gene expression. We confirmed several of the identified Rib targets by qRT-pCR and/or in situ hybridization. Our results indicate that Rib regulates cell growth and tissue shape in the Drosophila salivary gland via a diverse array of targets through both transcriptional activation and repression. Furthermore, our results suggest that autoregulation of rib expression may be a key component of the SG morphogenetic gene network.

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Section: Discussionmentioning

confidence: 99%

Ribbon regulates morphogenesis of the Drosophila embryonic salivary gland through transcriptional activation and repression

Loganathan

Lee

Wells

et al. 2016

Developmental Biology

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“…In contrast, activated Rac1 and Cdc42 are localized in pronounced plasma membrane blebs in cells migrating in collagen I. In 2D experiments, clear polarization of HUVECs has been shown, 28 but without any sign of blebbing. Treatment of cells with ML141 29 or the Rac1 inhibitor 553502 30 has additionally been shown to reduce directed cell migration in 2D settings.…”

Section: Discussionmentioning

confidence: 90%

New View on Endothelial Cell Migration

Kick

Nekolla

Rehberg

et al. 2016

ATVB

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A ngiogenesis, the formation of new blood vessels from pre-existing ones, is essential during development and wound healing and in diseases, such as cancer. Invasion into and migration through the extracellular matrix (ECM) are mandatory for endothelial cells (ECs) to assemble a vascular system. Thus, there is tremendous interest in understanding the properties and behavior of ECs in 3-dimensional (3D) environments.The basic concepts underlying EC migration have mostly been gleaned from observations in 2D cell culture systems. 1,2 However, the 3D environment encountered in vivo is far more complex. Cells have to integrate and coordinate their adhesion with the ECM and interpret attractive and repulsive cues to choose their pathway. 3,4 Many studies in recent years have revealed that different cell types use specific mechanisms to migrate into and navigate through the ECM. Studies in primary human fibroblasts showed that structurally distinct 3D environments support different modes of cell migration and that the polarization of phosphatidylinositol (3,4,5)-triphosphate and Rho family GTPase signaling differs between lobopodia-and lamellipodia-based 3D migration. 5 Studies on leukocyte motility and cancer cell migration in 3D environments revealed a switch between adhesion-dependent mesenchymal (elongated) and adhesion-independent amoeboid (rounded) cell motility in these cell types. Adhesion-independent motility is driven by actin polymerization and actomyosin contraction. 6,7 Plasma membrane blebbing was once primarily viewed as a by-product of apoptotic and necrotic processes. However, subsequent studies showed that cell blebbing is not limited to the execution of cell death programs 8,9 but is also implicated in cell movement. Plasma membrane blebs are now accepted as one of the types of cell protrusions mediating migration, similar to filopodia, lamellipodia, invadopodia, and podosomes. 10 However, which types of migration occur in ECs and whether ECs can switch between them remain largely unknown.ECMs are major components of the body's connective tissue and influence cellular functions, in addition to acting as a major reservoir of releasable growth factors and peptide mediators. These matrices vary in terms of fiber thickness, density, and stiffness as well as the pore size between fibers. The main ECM component of interstitial tissues is fibrillar collagen type © 2016 American Heart Association, Inc. Objective-Cell-matrix interactions are crucial for regulating cellular activities, such as migration. This is of special importance for morphogenic processes, such as angiogenesis (the development of new blood vessels). Most of our understanding of cell migration relies on 2-dimensional (2D) experiments. However, the awareness that 3D settings might elicit different results has increased. Knowledge about endothelial cell (EC) behavior in 3D environments and the influence of matrix composition on EC migration, in particular, is still limited. Approach and Results-We characterize the migration of single E...

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“…Immunoblotting was then performed as described previously [15]. For immunoprecipitation, cell lysates were incubated with antibody-conjugated agarose beads at 4°C for 2 hours.…”

Section: Methodsmentioning

confidence: 99%

CYLD Regulates RhoA Activity by Modulating LARG Ubiquitination

et al. 2013

Self Cite

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Rho family guanosine triphosphatases (GTPases), such as RhoA, Cdc42, and Rac1, play a fundamental role in various cellular processes. The activation of Rho proteins is catalyzed by guanine nucleotide-exchange factors (GEFs), which promote the exchange of GDP for GTP. The precise mechanisms regulating the activation of Rho proteins are not fully understood. Herein, we demonstrate that RhoA activity is regulated by cylindromatosis (CYLD), a deubiquitinase harboring multiple functions. In addition, we find that RhoA-mediated cytoskeletal rearrangement, chromosome separation, and cell polarization are altered in CYLD-depleted cells. Mechanistically, CYLD does not interact with RhoA; instead, it interacts with and deubiquitinates leukemia-associated RhoGEF (LARG). Our data further show that CYLD-mediated deubiquitination of LARG enhances its ability to stimulate the GDP/GTP exchange on RhoA. These data thus identify LARG as a new substrate of CYLD and provide novel insights into the regulation of RhoA activation. Our results also suggest that the LARG-RhoA signaling pathway may play a role in diverse CYLD-mediated cellular events.

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Regulation of Vascular Endothelial Cell Polarization and Migration by Hsp70/Hsp90-Organizing Protein

Cited by 37 publications

References 50 publications

Ribbon regulates morphogenesis of the Drosophila embryonic salivary gland through transcriptional activation and repression

Ribbon regulates morphogenesis of the Drosophila embryonic salivary gland through transcriptional activation and repression

New View on Endothelial Cell Migration

CYLD Regulates RhoA Activity by Modulating LARG Ubiquitination

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