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803条结果
  • 机译 维管植物中通过胞浆菌的细胞间通讯
    摘要:In plant development, cell-to-cell signaling is mediated by mobile signals, including transcription factors and small RNA molecules. This communication is essential for growth and patterning. Short-range movement of signals occurs in the extracellular space via the apoplastic pathway or directly from cell-to-cell via the symplastic pathway. Symplastic transport is mediated by plant specific structures called plasmodesmata, which are plasma membrane-lined pores that traverse the cell walls of adjacent cells thus connecting their cytoplasms. However, a thorough understanding of molecules moving via plasmodesmata and regulatory networks relying on symplastic signaling is lacking. Traffic via plasmodesmata is highly regulated, and callose turnover is known to be one mechanism. In Arabidopsis, plasmodesmata apertures can be regulated in a spatially and temporally specific manner with the icals3m, an inducible vector system expressing the mutated CalS3 gene encoding a plasmodesmata localized callose synthase that increases callose deposition at plasmodesmata. We discuss strategies to use the icals3m system for global analyses on symplastic signaling in plants.
  • 机译 ERK-ERF-EGR1,一种获得运动型表型的新型开关
    摘要:Unlike the well-characterized checkpoints of the cell cycle, which establish commitment to cell division, signaling pathways and gene expression programs that commit cells to migration are incompletely understood. Apparently, several molecular switches are activated in response to an extracellular cue, such as the epidermal growth factor (EGF), and they simultaneously confer distinct features of an integrated motile phenotype. Here we review such early (transcription-independent) and late switches, in light of a novel ERK-ERF-EGR1 switch we recently reported in the FASEB Journal. The study employed human mammary cells and two stimuli: EGF, which induced mammary cell migration, and serum factors, which stimulated cell growth. By contrasting the underlying pathways we unveiled a cascade that allows the active form of the ERK mitogen-activated protein kinase (MAPK) cascade to export the ERF repressor from the nucleus, thereby permitting tightly balanced stimulation of an EGR1-centered gene expression program.
  • 机译 洞察CRMP2(胶原蛋白介导蛋白2)在T淋巴细胞迁移中的作用
    摘要:Lymphocyte migration into the central nervous system is a critical step in the physiopathology of a variety of neurological diseases, including multiple sclerosis and virus-induced neuroinflammation. To better understand the molecular mechanisms involved in cells migration, we focused our studies on collapsin response mediator proteins (CRMPs), a group of phosphoproteins that mediate neural cell motility. There is now evidence that collapsin response mediator protein 2 (CRMP2) plays critical roles in the polarization (uropod formation) of T lymphocytes and their subsequent migration. CRMP2 was known to respond to semaphorin, ephrin and neurotrophin signaling in neurons. The link between the chemokine CXCL12, CRMP2 activity and cell migration has been demonstrated in T lymphocytes. These observations and comparisons of the activity of CRMPs in immune and non-immmune cells are summarized here. The ability of a human retrovirus to enhance lymphocyte migration through the modulation of CRMP2 activity is also discussed. In conclusion, viruses have the ability to manipulate the lymphocyte motility machinery, intensifying neural tissue invasion in infected patients.
  • 机译 层粘连蛋白家族
    摘要:
  • 机译 整联蛋白操纵以改善再生
    摘要:After central nervous system (CNS) insults, such as spinal cord injury or traumatic brain injury, neurons encounter a complex microenvironment where mechanisms that promote regeneration compete with inhibitory processes. Sprouting and axonal re-growth are key components of functional recovery, but are often counteracted by inhibitory molecules. Several strategies are being pursued whereby these inhibitory molecules are either being neutralized with blocking antibodies, with enzymatic degradation or downstream signaling events are being interfered with. Two recent studies, show that activating integrin signaling in dorsal root ganglion (DRG) neurons renders them able to overcome inhibitory signals, and could possibly lead to new strategies to improve neuronal regeneration.
  • 机译 内侧迁徙流
    摘要:Adult subventricular zone neurogenesis is an important process in most mammals. However, whether it persists in humans is highly debated. Recent work by Sanai and colleagues provides a major step in settling this debate. Using histological approaches, they demonstrated an active subventricular zone with limited neurogenesis in humans as well as discovered a new migratory route.
  • 机译 同源盒基因在血管形成和伤口愈合中的双重作用
    摘要:Homeobox genes represent a family of highly conserved transcription factors originally discovered to regulate organ patterning during development. More recently, several homeobox genes were shown to affect processes in adult tissue, including angiogenesis and wound healing. Whereas a subset of members of the Hox-family of homeobox genes activate growth and migration to promote angiogenesis or wound healing, other Hox genes function to restore or maintain quiescent, differentiated tissue function. Pathological tissue remodeling is linked to differential expression of activating or stabilizing Hox genes and dysregulation of Hox expression can contribute to disease progression. Studies aimed at understanding the role and regulation of Hox genes have provided insight into how these potent morphoregulatory genes can be applied to enhance tissue engineering or limit cancer progression.
  • 机译 细胞外基质在血管分支形态发生中的作用
    • 作者:Amel Mettouchi
    • 刊名:Cell Adhesion Migration
    • 2012年第6期
    摘要:Angiogenesis requires the development of a hierarchically branched network of vessels, which undergoes radial expansion and anastomosis to form a close circuit. Branching is achieved by coordinated behavior of endothelial cells that organize into leading “tip” cells and trailing “stalk” cells. Such organization is under control of the Dll4-Notch signaling pathway, which sets a hierarchy in receptiveness of cells to VEGF-A. Recent studies have shed light on a control of the Notch pathway by basement membrane proteins and integrin signaling, disclosing that extracellular matrix exerts active control on vascular branching morphogenesis. We will survey in the present review how extracellular matrix is a multifaceted substrate, which behind a classical structural role hides a powerful conductor function to shape the branching pattern of vessels.
  • 机译 VEGF引发的血管生成和uPA / uPAR系统
    摘要:Angiogenesis involves a series of tightly regulated cellular processes initiated primarily by the vascular endothelial growth factor (VEGF). The urokinase-type plasminogen activator system, consisting of the urokinase-type plasminogen activator (uPA), its cellular receptor uPAR and its inhibitor PAI-1, participates in the realization of these VEGF-induced processes by activating pericellular proteolysis, increasing vascular permeability and by supporting endothelial cell proliferation and migration.
  • 机译 信号量和VEGF在突触发生和突触可塑性中的新兴作用
    摘要:Synapse formation, maintenance and plasticity are critical for the correct function of the nervous system and its target organs. During development, these processes enable the establishment of appropriate neural circuits. During adulthood, they allow adaptation to both physiological and environmental changes. In this review, we discuss emerging roles for two families of classical axon and vascular guidance cues in synaptogenesis and synaptic plasticity, the semaphorins and the vascular endothelial growth factors (VEGFs). Their contribution to synapse formation and function add a new facet to the spectrum of overlapping and complementary roles for these molecules in development, adulthood and disease.
  • 机译 VEGF在乳腺癌细胞中的自分泌功能
    摘要:Vascular endothelial growth factor A (VEGF-A) is well known for its key roles in blood vessel growth. Although most studies on VEGF and VEGF receptors have been focused on their functions in angiogenesis and in endothelial cells, the role of VEGF in cancer biology appears as an emerging area of importance. In this context, the presence of VEGF receptors in tumor cells strongly suggests that VEGF-A also promotes a wide range of functions, both in vitro and in vivo, all autocrine functions on tumor cells, including adhesion, survival, migration and invasion. Ultimately, refining our knowledge of VEGF signaling pathways in tumor cells should help us to understand why the current used treatments targeting the VEGF pathway in cancer are not universally effective in inhibiting metastasis tumors, and it should also provide new avenues for future therapies.
  • 机译 通过VEGF /神经纤维蛋白信号传导增强整合素功能
    摘要:This review advances the hypothesis that the ability of integrins to engage their extracellular matrix ligands and signal can be regulated in tumor cells by vascular endothelial growth factor (VEGF), a major angiogenic factor that also has direct effects on the function of tumor cells. More specifically, we will discuss how neuropilins (NRPs), a distinct class of VEGF receptors, enable the function of specific integrins that contribute to tumor initiation and progression.
  • 机译 VEGF165b在病理生理中的作用
    摘要:Anti-angiogenic vascular endothelial growth factor A (VEGF)165b and pro-angiogenic VEGF165 are generated from the same transcript, and their relative amounts are dependent on alternative splicing. The role of VEGF165b has not been investigated in as much detail as VEGF165, although it appears to be highly expressed in non-angiogenic tissues and, in contrast with VEGF165, is downregulated in tumors and other pathologies associated with abnormal neovascularization such as diabetic retinopathy or Denys Drash syndrome. VEGF165b inhibits VEGFR2 signaling by inducing differential phosphorylation, and it can be used to block angiogenesis in in vivo models of tumorigenesis and angiogenesis-related eye disease. Recent reports have identified three serine/arginine-rich proteins, SRSF1, SRSF2 and SRSF6, and studied their role in regulating terminal splice-site selection. Since the balance of VEGF isoforms is lost in cancer and angiogenesis-related conditions, control of VEGF splicing could also be used as a basis for therapy in these diseases.
  • 机译 VEGF水平和微环境的血管生成潜力可影响结直肠肝转移的手术策略
    摘要:The hypotheses emerging from basic research on colorectal liver metastases must be tested in clinical situations for the adaptation of current treatment strategies. Pre-metastatic niches have been shown to exist in human colorectal synchronous metastases, with the liver parenchyma adjacent to the synchronous liver metastases providing a favorable, angiogenic environment for metastatic tumor growth. The role of the VEGF signaling pathway in liver regeneration and tumor growth remains unclear, but the use of antiangiogenic agents in combination with surgical treatment is almost certainly beneficial.
  • 机译 微模板印刷法分离不同的粘附复合物和相关的细胞骨架
    摘要:Adhesion between cells and the extracellular matrix is mediated by different types of transmembraneous proteins. Their associations to specific partners lead to the assembly of contacts such as focal adhesions and hemidesmosomes. The spatial overlap between both contacts within cells has however limited the study of each type of contact. Here we show that with “stampcils” focal contacts and hemidesmosomes can be spatially separated: cells are plated within the cavities of a stencil and the grids of the stencil serve as stamps for grafting an extracellular matrix protein—fibronectin. Cells engage new contacts on stamped zones leading to the segregation of adhesions and their associated cytoskeletons, i.e., actin and intermediate filaments of keratins. This new method should provide new insights into cell contacts compositions and dynamics.
  • 机译 肌动蛋白
    摘要:Here, we present emerging ideas surrounding the interplay between the actin cytoskeleton and receptor transport and activation. The bulk of actin dynamics in cells is thought to contribute to architecture and mobility. Actin also contributes to trafficking, acting as a molecular scaffold, providing force to deform membranes, facilitating vesicle abscission or propelling a vesicle through the cytoplasm, and recent studies highlight important connections between the directed trafficking of receptors and the impact on cell migration and actin dynamics. Additionally, a number of newly described actin nucleation promoting factors, such as the vesicle associated protein WASH, reveal unexpected roles of actin in membrane traffic and suggest that the cell dedicates a significant proportion of its regulation of actin dynamics to controlling trafficking.
  • 机译 鸟嘌呤核苷酸交换因子三重奏的许多面孔
    摘要:Small Rho-GTPases are enzymes that are bound to GDP or GTP, which determines their inactive or active state, respectively. The exchange of GDP for GTP is catalyzed by so-called Rho-guanine nucleotide exchange factors (GEFs). Rho-GEFs are characterized by a Dbl-homology (DH) and adjacent Pleckstrin-homology (PH) domain that serves as enzymatic unit for the GDP/GTP exchange. Rho-GEFs show different GTPase specificities, meaning that a particular GEF can activate either multiple GTPases or only one specific GTPase. We recently reported that the Rho-GEF Trio, known to be able to exchange GTP on Rac1, RhoG and RhoA, regulates lamellipodia formation to mediate cell spreading and migration in a Rac1-dependent manner. In this commentary, we review the current knowledge of Trio in several aspects of cell biology.
  • 机译 癌相关基质成纤维细胞的唤醒
    摘要:Cancer-associated fibroblasts (CAF), comprised of activated fibroblasts or myofibroblasts, are found in stroma surrounding solid tumors; these myofibroblasts promote invasion and metastasis of cancer cells. Activation of stromal fibroblasts into myofibroblasts is induced by expression of cystoskeleton protein, palladin, at early stages in tumorigenesis and increases with neoplastic progression. Expression of palladin in fibroblasts is triggered by paracrine signaling from adjacent k-ras-expressing epithelial cells. Three-dimensional co-cultures of palladin-expressing fibroblasts and pancreatic cancer cells reveals that the activated fibroblasts lead the invasion by creating tunnels through the extracellular matrix through which the cancer cells follow. Invasive tunneling occurs as a result of the development of invadopodia-like cellular protrusions in the palladin-activated fibroblasts and the addition of a wounding/inflammatory trigger. Abrogation of palladin reduces the invasive capacity of these cells. CAF also play a role in cancer resistance and immuno-privilege, making the targeting of activators of these cells of interest for oncologists.
  • 机译 G蛋白偶联受体激酶2(GRK2)和组蛋白脱乙酰基酶6(HDAC6)在上皮细胞运动十字路口之间的相互作用
    摘要:G protein-coupled receptor kinase 2 (GRK2) is emerging as a key integrative node in cell migration control. In addition to its canonical role in the desensitization of G protein-coupled receptors involved in chemotaxis, novel recently identified GRK2 substrates and interacting partners appear to mediate the GRK2-dependent modulation of diverse molecular processes involved in motility, such as gradient sensing, cell polarity or cytoskeletal reorganization. We have recently identified an interaction between GRK2 and histone deacetylase 6 (HDAC6), a major cytoplasmic α-tubulin deacetylase involved in cell motility and adhesion. GRK2 dynamically associates with and phosphorylates HDAC6 to stimulate its α-tubulin deacetylase activity at specific cellular localizations such as the leading edge of migrating cells, thus promoting local tubulin deacetylation and enhanced motility. This GRK2-HDAC6 functional interaction may have important implications in pathological contexts related to aberrant epithelial cell migration.
  • 机译 Paxillin响应物理提示控制定向细胞运动
    摘要:Physical cues from the extracellular environment that influence cell shape and directional migration are transduced into changes in cytoskeletal organization and biochemistry through integrin-based cell adhesions to extracellular matrix (ECM). Paxillin is a focal adhesion (FA) scaffold protein that mediates integrin anchorage to the cytoskeleton, and has been implicated in regulation of FA assembly and cell migration. To determine whether paxillin is involved in coupling mechanical distortion with directional movement, cell shape was physically constrained by culturing cells on square-shaped fibronectin-coated adhesive islands surrounded by non-adhesive barrier regions that were created with a microcontact printing technique. Square-shaped cells preferentially formed FAs and extended lamellipodia from their corner regions when stimulated with PDGF, and loss of paxillin resulted in loss of this polarized response. Selective expression of the N- and C-terminal domains of paxillin produced opposite, but complementary, effects on suppressing or promoting lamellipodia formation in different regions of square cells, which corresponded to directional motility defects in vitro. Paxillin loss or mutation was also shown to affect the formation of circular dorsal ruffles, and this corresponded to changes in cell invasive behavior in 3D. This commentary addresses the implications of these findings in terms of how a multifunctional FA scaffold protein can link physical cues to cell adhesion, protrusion and membrane trafficking so as to control directional migration in 2D and 3D. We also discuss how microengineered ECM islands and in vivo model systems can be used to further elucidate the functions of paxillin in directional migration.

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