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When an action potential reaches the presynaptic axon terminal, it releases neurotransmitters from the neuron into the synaptic cleft at a chemical synapse. The released neurotransmitter can be excitatory or inhibitory. The critical criteria commonly used to determine whether a molecule is a neurotransmitter at a chemical synapse are the molecule's presence in the presynaptic neuron. Second, its release is in response to strong presynaptic depolarization. And lastly, the presence of...
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Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
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Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking...
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El factor EJC eIF4AIII modula la fuerza sináptica y la expresión de proteínas neuronales.

Corinna Giorgi1, Gene W Yeo, Martha E Stone

  • 1Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02454, USA.

Cell
|July 17, 2007
PubMed
Resumen

El complejo de unión de exones (EJC) proteína eIF4AIII regula la síntesis de proteínas neuronales. Su agotamiento mejora la fuerza sináptica y la abundancia de receptores AMPA, lo que sugiere un papel en la plasticidad sináptica.

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Área de la Ciencia:

  • La neurociencia es la neurociencia.
  • Biología Molecular Biología Molecular
  • Biología celular Biología celular.

Sus antecedentes:

  • La función neuronal y la plasticidad sináptica dependen de la traducción controlada del ARNm en las dendritas.
  • El complejo de unión de exones (EJC) de la proteína eIF4AIII está involucrado en el procesamiento y transporte del ARNm.

Objetivo del estudio:

  • Investigar el papel de eIF4AIII en los gránulos de ARNm neuronal y en los ARNm dendríticos.
  • Para determinar el impacto de eIF4AIII en la fuerza sináptica, la abundancia de los receptores AMPA y los niveles de proteínas ARC.

Principales métodos:

  • Asociación de eIF4AIII con gránulos de ARNm neuronal y ARNm dendrítico.
  • Destrucción de eIF4AIII en las neuronas.
  • Medición de la fuerza sináptica y abundancia del receptor AMPA GLUR1.
  • Análisis de la proteína ARC y los niveles de ARNm del arco.
  • Identificación computacional de candidatos a la desintegración mediada por el no sentido (NMD).

Principales resultados:

  • eIF4AIII está localizado en los gránulos neuronales de ARNm y en los ARNm dendríticos.
  • eIF4AIII knockdown aumenta significativamente la fuerza sináptica y la abundancia del receptor AMPA GLUR1.
  • El agotamiento de eIF4AIII eleva los niveles de proteína ARC, que es crucial para la potenciación a largo plazo.
  • ARNm de arco, abundante en las dendritas, se identifica como un objetivo para NMD.
  • Se descubrieron de forma computacional nuevos candidatos a NMD que afectan la actividad sináptica.

Conclusiones:

  • eIF4AIII juega un papel crítico en la regulación de la síntesis de proteínas en las sinapsis.
  • Las vías de desintegración dependientes de la traducción, como la NMD, pueden actuar como reguladores esenciales de la síntesis de proteínas en las neuronas.
  • Estos hallazgos proporcionan información sobre los mecanismos que controlan la expresión de proteínas restringidas espacial y temporalmente en las neuronas.