VE-Cadherin Signaling Induces EB3 Phosphorylation to Suppress Microtubule Growth and Assemble Adherens Junctions

Komarova, Yulia; Huang, Fei; Geyer, Melissa; Daneshjou, Nazila; Garcia, Alexander N.; Idalino, Luiza; Kreutz, Barry; Mehta, Dolly; Malik, Asrar B.

doi:10.1016/j.molcel.2012.10.011

Cited by 50 publications

(69 citation statements)

References 62 publications

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“…Our results support the hypothesis that the reduced MT dynamics at N-cadherin-mediated contacts results from an inhibitory action of N-cadherin engagement, rather than from the absence of a positive signal provided by integrins, as reported for VE-cadherin engagement (Komarova et al, 2012). Indeed, the reduction of MT growth rate can be alleviated by the expression of a truncated form of N-cadherin, which interferes with the function of this protein by sequestering catenins and thus destabilizing cadherin adhesion complexes.…”

Section: Discussionsupporting

confidence: 90%

“…Indeed, cell-cell contact morphology, dynamics and stability are very different in epithelial and myogenic cells, the former presenting a fibroblastic phenotype with poorly differentiated cell-cell contacts that are devoid of true adherens junctions (Mège et al, 2006). By contrast, a negative-feedback loop has also been reported very recently between vascular-endothelial (VE)-cadherin-mediated contacts and MT growth in endothelial cells (Komarova et al, 2012). In addition, we observed that MTs were also repelled from cadherin adhesions formed by epithelial MDCK cells on an E-cadherin-Fc substrate.…”

Section: Discussionsupporting

confidence: 56%

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Adhesive interactions of N-cadherin limit the recruitment of microtubules to cell–cell contacts through organization of actomyosin

Plestant¹,

Strale²,

Seddiki³

et al. 2014

Development

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Adhesive interactions of cadherins induce crosstalk between adhesion complexes and the actin cytoskeleton, allowing strengthening of adhesions and cytoskeletal organization. The underlying mechanisms are not completely understood, and microtubules (MTs) might be involved, as for integrin-mediated cell-extracellular-matrix adhesions. Therefore, we investigated the relationship between N-cadherin and MTs by analyzing the influence of N-cadherin engagement on MT distribution and dynamics. MTs progressed less, with a lower elongation rate, towards cadherin adhesions than towards focal adhesions. Increased actin treadmilling and the presence of an actomyosin contractile belt, suggested that actin relays inhibitory signals from cadherin adhesions to MTs. The reduced rate of MT elongation, associated with reduced recruitment of end-binding (EB) proteins to plus ends, was alleviated by expression of truncated N-cadherin, but was only moderately affected when actomyosin was disrupted. By contrast, destabilizing actomyosin fibers allowed MTs to enter the adhesion area, suggesting that tangential actin bundles impede MT growth independently of MT dynamics. Blocking MT penetration into the adhesion area strengthened cadherin adhesions. Taken together, these results establish a crosstalk between N-cadherin, Factin and MTs. The opposing effects of cadherin and integrin engagement on actin organization and MT distribution might induce bias of the MT network during cell polarization.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 56%

Adhesive interactions of N-cadherin limit the recruitment of microtubules to cell–cell contacts through organization of actomyosin

Plestant¹,

Strale²,

Seddiki³

et al. 2014

Development

View full text Add to dashboard Cite

show abstract

“…146 They can form homo-or heterodimers. 147 Komarova et al 148 recently identified a key role of EB3 in regulating AJs adhesion by stabilizing MTs. They showed that phosphorylation of EB3 at S162 induced MT growth in confluent endothelial monolayers, which disassembled AJs.…”

Section: Role Of End-binding Proteinsmentioning

confidence: 99%

Mechanisms Regulating Endothelial Permeability

et al. 2014

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The endothelial monolayer partitioning underlying tissue from blood components in the vessel wall maintains tissue fluid balance and host defense through dynamically opening intercellular junctions. Edemagenic agonists disrupt endothelial barrier function by signaling the opening of the intercellular junctions leading to the formation of protein-rich edema in the interstitial tissue, a hallmark of tissue inflammation that, if left untreated, causes fatal diseases, such as acute respiratory distress syndrome. In this review, we discuss how intercellular junctions are maintained under normal conditions and after stimulation of endothelium with edemagenic agonists. We have focused on reviewing the new concepts dealing with the alteration of adherens junctions after inflammatory stimulus.

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“…Images were acquired every 3 s. Microtubule growth was analyzed using a plusTipTracker software package on 55-65 frames (Matov et al, 2010). Tracking control parameters were as described previously (Komarova et al, 2012). The 'Quadrant Scatter Plot' tool, a part of plusTipTracker package, was used to determine the relationship between growth rate and growth lifetime and to divide microtubules into four subpopulations based on deviation from mean growth speed and growth lifetime (Applegate et al, 2011).…”

Section: Microtubule Dynamicsmentioning

confidence: 99%

KIF13B regulates angiogenesis through golgi-plasma membrane trafficking of VEGFR2

Yamada

Nakajima

Geyer

et al. 2014

Journal of Cell Science

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Although the trafficking of newly synthesized VEGFR2 to the plasma membrane is a key determinant of angiogenesis, the molecular mechanisms of Golgi to plasma membrane trafficking are unknown. Here, we have identified a key role of the kinesin family plus-end molecular motor KIF13B in delivering VEGFR2 cargo from the Golgi to the endothelial cell surface. KIF13B is shown to interact directly with VEGFR2 on microtubules. We also observed that overexpression of truncated versions of KIF13B containing the binding domains that interact with VEGFR2 inhibited VEGF-induced capillary tube formation. KIF13B depletion prevented VEGFmediated endothelial migration, capillary tube formation and neovascularization in mice. Impairment in trafficking induced by knockdown of KIF13B shunted VEGFR2 towards the lysosomal degradation pathway. Thus, KIF13B is an essential molecular motor required for the trafficking of VEGFR2 from the Golgi, and its delivery to the endothelial cell surface mediates angiogenesis.

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VE-Cadherin Signaling Induces EB3 Phosphorylation to Suppress Microtubule Growth and Assemble Adherens Junctions

Cited by 50 publications

References 62 publications

Adhesive interactions of N-cadherin limit the recruitment of microtubules to cell–cell contacts through organization of actomyosin

Adhesive interactions of N-cadherin limit the recruitment of microtubules to cell–cell contacts through organization of actomyosin

Mechanisms Regulating Endothelial Permeability

KIF13B regulates angiogenesis through golgi-plasma membrane trafficking of VEGFR2

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