Plants deploy numerous plasma membrane receptors to sense and rapidly react to environmental changes. Correct localization and adequate protein levels of the cell-surface receptors are critical for signaling activatio...Plants deploy numerous plasma membrane receptors to sense and rapidly react to environmental changes. Correct localization and adequate protein levels of the cell-surface receptors are critical for signaling activation and modulation of plant development and defense against pathogens. After ligand binding, receptors are internalized for degradation and signaling attenuation. However, one emerging notion is that the Iigand-induced endocytosis of reCeptor complexes is important for the signal duration, amplitude, and specificity. Recently, mutants of maior endocytosis players, including clathrin and dynamin, have been shown to display defects in activation of a subset of signal transduction pathways, implying that signaling in plants might not be solely restricted to the plasma membrane. Here, we summarize the up-to-date knowledge of receptor complex endocytosis and its effect on the signaling outcome, in the context of plant development and immunity.展开更多
Extracellular vesicles(EVs)have recently received much attention about the application of drug carriers due to their desirable properties such as nano-size,biocompatibility,and high stability.Herein,we demonstrate ora...Extracellular vesicles(EVs)have recently received much attention about the application of drug carriers due to their desirable properties such as nano-size,biocompatibility,and high stability.Herein,we demonstrate orange-derived extracellular vesicles(OEV)nanodrugs(DN@OEV)by modifying cRGD-targeted doxorubicin(DOX)nanoparticles(DN)onto the surface of OEV,enabling significantly enhancing tumor accumulation and penetration,thereby efficiently inhibiting the growth of ovarian cancer.The obtained DN@OEV enabled to inducement of greater transcytosis capability in ovarian cancer cells,which presented the average above 10-fold transcytosis effect compared with individual DN.It was found that DN@OEV could trigger receptor-mediated endocytosis to promote early endosome/recycling endosomes pathway for exocytosis and simultaneously reduce degradation in the early endosomes-late endosomes-lysosome pathway,thereby inducing the enhanced transcytosis.In particular,the zombie mouse model bearing orthotopic ovarian cancer further validated DN@OEV presented high accumulation and penetration in tumor tissue by the transcytosis process.Our study indicated the strategy in enhancing transcytosis has significant implications for improving the therapeutic efficacy of thedrugdelivery system.展开更多
In this work,a three-dimensional axisymmetric model with nanoparticle,receptor-ligand bonds and cell membrane as a system was used to study the quasi-static receptor-mediated endocytosis process of spherical nanoparti...In this work,a three-dimensional axisymmetric model with nanoparticle,receptor-ligand bonds and cell membrane as a system was used to study the quasi-static receptor-mediated endocytosis process of spherical nanoparticles in drug delivery.The minimization of the system energy function was carried out numerically,and the deformations of nanoparticle,receptor-ligand bonds and cell membrane were predicted.Results show that passive endocytosis may fail due to the rupture of receptor-ligand bonds during the wrapping process,and the size and rigidity of nanoparticles affect the total deformation energy and the terminal wrapping stage.Our results suggest that,in addition to the energy requirement,the success of passive endocytosis also depends on the maximum strength of the receptor-ligand bonds.展开更多
基金supported by the Research Foundation-Flanders(G008416N)
文摘Plants deploy numerous plasma membrane receptors to sense and rapidly react to environmental changes. Correct localization and adequate protein levels of the cell-surface receptors are critical for signaling activation and modulation of plant development and defense against pathogens. After ligand binding, receptors are internalized for degradation and signaling attenuation. However, one emerging notion is that the Iigand-induced endocytosis of reCeptor complexes is important for the signal duration, amplitude, and specificity. Recently, mutants of maior endocytosis players, including clathrin and dynamin, have been shown to display defects in activation of a subset of signal transduction pathways, implying that signaling in plants might not be solely restricted to the plasma membrane. Here, we summarize the up-to-date knowledge of receptor complex endocytosis and its effect on the signaling outcome, in the context of plant development and immunity.
基金supported by the National Natural Science Foundation of China(22275080,22075127,and 82073340)the Natural Science Foundation of Guangdong Province(2022A 1515012044,China).
文摘Extracellular vesicles(EVs)have recently received much attention about the application of drug carriers due to their desirable properties such as nano-size,biocompatibility,and high stability.Herein,we demonstrate orange-derived extracellular vesicles(OEV)nanodrugs(DN@OEV)by modifying cRGD-targeted doxorubicin(DOX)nanoparticles(DN)onto the surface of OEV,enabling significantly enhancing tumor accumulation and penetration,thereby efficiently inhibiting the growth of ovarian cancer.The obtained DN@OEV enabled to inducement of greater transcytosis capability in ovarian cancer cells,which presented the average above 10-fold transcytosis effect compared with individual DN.It was found that DN@OEV could trigger receptor-mediated endocytosis to promote early endosome/recycling endosomes pathway for exocytosis and simultaneously reduce degradation in the early endosomes-late endosomes-lysosome pathway,thereby inducing the enhanced transcytosis.In particular,the zombie mouse model bearing orthotopic ovarian cancer further validated DN@OEV presented high accumulation and penetration in tumor tissue by the transcytosis process.Our study indicated the strategy in enhancing transcytosis has significant implications for improving the therapeutic efficacy of thedrugdelivery system.
基金This work was supported by the National Natural Science Foundations of China(11372191,11232010)the Natural Science and Engineering Research Council of Canada.
文摘In this work,a three-dimensional axisymmetric model with nanoparticle,receptor-ligand bonds and cell membrane as a system was used to study the quasi-static receptor-mediated endocytosis process of spherical nanoparticles in drug delivery.The minimization of the system energy function was carried out numerically,and the deformations of nanoparticle,receptor-ligand bonds and cell membrane were predicted.Results show that passive endocytosis may fail due to the rupture of receptor-ligand bonds during the wrapping process,and the size and rigidity of nanoparticles affect the total deformation energy and the terminal wrapping stage.Our results suggest that,in addition to the energy requirement,the success of passive endocytosis also depends on the maximum strength of the receptor-ligand bonds.
