Video Experimental Relacionado
Updated: Nov 2, 2025
10:59
Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET
Published on: August 17, 2022
3.4K
GluD1 es un dispositivo de transducción de señales disfrazado de receptor ionotrópico
Jinye Dai1,2, Christopher Patzke3,4, Kif Liakath-Ali3
1Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. jydai@stanford.edu.
Nature
|June 17, 2021
Resumen
Los receptores delta de glutamato (GluDs) regulan la actividad de los receptores NMDA y AMPA mediante la conversión directa de las señales de la neurexina-cerebellina en respuestas postsinápticas, evitando su función ionotrópica.
Área de la Ciencia:
- La neurociencia
- Biología molecular
- Plasticidad sináptica
Sus antecedentes:
- Los receptores ionotrópicos del glutamato delta 1 y 2 (GluD1/ 2) forman complejos de adhesión transsinápticos con las neurexinas a través de las cerebelinas.
- La función precisa de estos complejos de neurexina-cerebellina-GluD en la adhesión sináptica frente a la señalización sigue sin estar clara.
Objetivo del estudio:
- Investigar el papel de GluD1 en la mediación de la señalización trans-sináptica en las sinapsis del hipocampo.
- Para aclarar el mecanismo por el cual los complejos de neurexina-cerebelina regulan la actividad del receptor de glutamato.
Principales métodos:
- Se utilizaron sinapsis del hipocampo para estudiar la interacción entre las neurexinas presinápticas y la GluD1 postsináptica.
- Se emplean construcciones mínimas GluD1/2 para diseccionar dominios funcionales.
- Analizó la regulación diferencial de los receptores NMDA y AMPA.
Principales resultados:
- Los complejos presinápticos de neurexina y cerebelina que se unen a la GluD1 postsináptica controlan la actividad de los receptores de glutamato sin alterar el número de sinapsis.
- Los complejos de neurexina-1-cerebellina-2 y neurexina-3-cerebellina-2 regulan diferencialmente los receptores NMDA y AMPA a través de distintas señales del efector GluD1.
- Las construcciones mínimas de GluD1/2 que contienen solo dominios de unión y citoplasma regulan los niveles de los receptores NMDA y AMPA, lo que indica un papel de señalización independiente de la función ionotrópica.
Conclusiones:
- GluD1/2 funcionan como moléculas de señalización, no sólo como moléculas de adhesión.
- Un nuevo mecanismo de transducción evita la arquitectura ionotrópica de las GluD para convertir las señales de neurexina-cerebellina extracelular en respuestas de receptores postsinápticos.
- Las secuencias específicas en los sitios de empalme de la neurexina y los dominios citoplasmáticos de GluD dictan la especificidad de la señalización.
Videos de Conceptos Relacionados
01:21G-Protein Gated Ion Channels
5.1K
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
Sensory...
5.1K
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
3.1K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
3.1K
01:22Amplifying Signals via Enzymatic Cascade
14.6K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
14.6K
01:22Activation and Inactivation of G Proteins
8.2K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
8.2K
01:19Ligand-gated Ion Channels
13.3K
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
13.3K
01:30Transducer Mechanism: G Protein–Coupled Receptors
3.1K
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
GPCRs are also called heptahelical,...
3.1K