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Videos de Conceptos Relacionados

Cell Migration01:09

Cell Migration

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Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
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G Protein-coupled Receptors01:15

G Protein-coupled Receptors

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G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
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Cytoskeletal Coordination in Cell Migration01:32

Cytoskeletal Coordination in Cell Migration

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A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
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Cell Polarization by Rho Proteins01:21

Cell Polarization by Rho Proteins

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Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
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G-protein Coupled Receptors01:21

G-protein Coupled Receptors

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G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
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Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

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Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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Video Experimental Relacionado

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Imaging G-protein Coupled Receptor GPCR-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
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Estructura del complejo del receptor GPC3-Unc5 y su papel en la migración celular

Onno Akkermans1, Céline Delloye-Bourgeois2, Claudia Peregrina3

  • 1Department of Biochemistry, University of Oxford, Oxford, UK.

Cell
|October 14, 2022
PubMed
Resumen

Este estudio revela la estructura del receptor Uncoordinated-5 D (Unc5D) unido al glypican-3 (GPC3), descubriendo cómo sus interacciones guían la migración de las células neurales y la diseminación de las células cancerosas.

Palabras clave:
GPC3 para el tratamiento de las enfermedadesUNC5A (en inglés)En el caso de los vehículos de motor:UNC5CUNC5D (en inglés)Unidad 5guía de la célulaMigración celulardesarrollo de la cortezaLa cristalografíaglicano-3 y sus derivadosLos nanocuerposel neuroblastomaPrueba de rayasBiología estructuralResonancia plasmónica de superficieNo coordinado-5

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Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
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Ex Vivo Imaging of Postnatal Cerebellar Granule Cell Migration Using Confocal Macroscopy
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Ex Vivo Imaging of Postnatal Cerebellar Granule Cell Migration Using Confocal Macroscopy

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Área de la Ciencia:

  • La neurociencia
  • Biología estructural
  • Biología del cáncer

Sus antecedentes:

  • La migración neuronal es crucial para el desarrollo del cerebro, involucrando a los receptores de guía de la superficie celular.
  • Las células cancerosas explotan estos mecanismos de desarrollo para la metástasis.

Objetivo del estudio:

  • Para aclarar la base estructural de las interacciones del receptor Uncoordinated-5 D (Unc5D) y el glypican-3 (GPC3).
  • Comprender el papel de los complejos Unc5D-GPC3 en la orientación celular durante el desarrollo y el cáncer.

Principales métodos:

  • Cristalografía de rayos X para determinar la estructura del complejo octamérico.
  • Simulaciones de dinámica molecular y espectrometría de masas para su validación.
  • Mutagenesis basada en la estructura y ensayos de nanocuerpos en modelos de ratón y xenotransplante.

Principales resultados:

  • Las estructuras cristalinas revelaron un complejo octamérico Unc5D-GPC3 con interacciones centrales glicano-glicano.
  • Los glicanos ligados a N de GPC3 y los triptófanos C-manosilados de Unc5D median la unión.
  • Se demostró que las interacciones Unc5D-GPC3 guían la migración de las neuronas piramidal y la diseminación de las células del neuroblastoma.

Conclusiones:

  • Se demostró un mecanismo estructural conservado para la orientación celular mediada por las interacciones Unc5D-GPC3.
  • La unión de Unc5D-GPC3 finamente equilibrada es crítica para regular la migración celular tanto en el desarrollo como en la enfermedad.