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Aude Guillabert-Gourgues Beatrice Jaspard-Vinassa Marie-Lise Bats Raj N. Sewduth Nathalie Franzl Claire Peghaire Sylvie Jeanningros Catherine Moreau Etienne Roux Frederic Larrieu-Lahargue Pascale Dufourcq Thierry Couffinhal Cecile Duplàa 《Molecular biology of the cell》2016,27(6):941-953
Angiogenesis involves the coordinated growth and migration of endothelial cells (ECs) toward a proangiogenic signal. The Wnt planar cell polarity (PCP) pathway, through the recruitment of Dishevelled (Dvl) and Dvl-associated activator of morphogenesis (Daam1), has been proposed to regulate cell actin cytoskeleton and microtubule (MT) reorganization for oriented cell migration. Here we report that Kif26b—a kinesin—and Daam1 cooperatively regulate initiation of EC sprouting and directional migration via MT reorganization. First, we find that Kif26b is recruited within the Dvl3/Daam1 complex. Using a three-dimensional in vitro angiogenesis assay, we show that Kif26b and Daam1 depletion impairs tip cell polarization and destabilizes extended vascular processes. Kif26b depletion specifically alters EC directional migration and mislocalized MT organizing center (MTOC)/Golgi and myosin IIB cell rear enrichment. Therefore the cell fails to establish a proper front–rear polarity. Of interest, Kif26b ectopic expression rescues the siDaam1 polarization defect phenotype. Finally, we show that Kif26b functions in MT stabilization, which is indispensable for asymmetrical cell structure reorganization. These data demonstrate that Kif26b, together with Dvl3/Daam1, initiates cell polarity through the control of PCP signaling pathway–dependent activation. 相似文献
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Cecile?M. Perrault Agusti Brugues Elsa Bazellieres Pierre Ricco Damien Lacroix Xavier Trepat 《Biophysical journal》2015,109(8):1533-1536
Endothelial cells are constantly exposed to fluid shear stresses that regulate vascular morphogenesis, homeostasis, and disease. The mechanical responses of endothelial cells to relatively high shear flow such as that characteristic of arterial circulation has been extensively studied. Much less is known about the responses of endothelial cells to slow shear flow such as that characteristic of venous circulation, early angiogenesis, atherosclerosis, intracranial aneurysm, or interstitial flow. Here we used a novel, to our knowledge, microfluidic technique to measure traction forces exerted by confluent vascular endothelial cell monolayers under slow shear flow. We found that cells respond to flow with rapid and pronounced increases in traction forces and cell-cell stresses. These responses are reversible in time and do not involve reorientation of the cell body. Traction maps reveal that local cell responses to slow shear flow are highly heterogeneous in magnitude and sign. Our findings unveil a low-flow regime in which endothelial cell mechanics is acutely responsive to shear stress. 相似文献
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Parasites are ubiquitous in nature and can be costly to animal fitness, so hosts have evolved behavioural counter-strategies to mitigate infection risk. We investigated feeding-related infection-avoidance strategies in Japanese macaques via field-experimentation and observation. We first examined risk sensitivity during foraging tasks involving faecally contaminated or debris-covered food items, and then investigated individual tendencies to manipulate food items during natural foraging bouts. We concurrently monitored geohelminth infection in all subjects. We ran a principal component analysis on the observational/experimental data to generate a hygienic index across individuals and found that hygienic tendencies towards faeces avoidance and food manipulation correlated negatively with geohelminth infection. Females scored higher in hygienic tendencies than males, which might contribute to the common vertebrate pattern of male-biased infection. The behavioural tendencies observed may reflect a general form of hygiene, providing a mechanism of behavioural immunity against parasites with implications for the evolution and diversification of health maintenance strategies in humans. 相似文献
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Cecile Gache Yolande Berthois Pierre-Marie Martin Simone Saez 《In vitro cellular & developmental biology. Animal》1998,34(4):347-351
Summary In the mammary gland, mesenchymal-epithelial interactions are of paramount importance during normal and tumoral developments.
We have studied the paracrine growth regulation of a variety of breast epithelial cells in coculture with normal or pathological
breast fibroblasts. Two models of coculture were used in which the two cell types were seeded and grown, either together in
microchamber slides or separated by a microporous membrane. Under these two conditions, all fibroblasts were shown to stimulate
the proliferation of the hormono-responsive breast carcinoma MCF-7 cell line, suggesting that cell contacts were not indispensable
for the paracrine stimulation of MCF-7 cell growth by fibroblasts. Moreover, in the Transwell coculture system, the proliferation
of a variety of other breast carcinoma cells (MDA-MB231, T47D, and BT-20) was also stimulated by fibroblasts. However, the
amplitude of the proliferative response seemed to be dependent on the carcinoma cell line considered. Moreover, the proliferative
response of normal mammary epithelial cells to the presence of fibroblasts was shown to be significantly higher than the tumor
cell response. The nature of the tissue of fibroblast origin, normal or pathological, did not influence the growth response
of the epithelial cells. In this study, we thus demonstrate that fibroblasts are able to stimulate the proliferation of normal
and carcinoma cells through paracrine exchange mechanisms. We also conclude that the target epithelial cell phenotype will
essentially determine the extent of the proliferative response. 相似文献
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