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Influencia de la posición de la vesícula sináptica en la probabilidad de liberación y el modo de fusión exocitótica
Hyokeun Park1, Yulong Li, Richard W Tsien
1Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA.
Science (New York, N.Y.)
|February 21, 2012
Resumen
Los investigadores desarrollaron un nuevo método para rastrear vesículas sinápticas individuales en tiempo real, revelando cómo su posición y movimiento influyen en la neurotransmisión y los modos de fusión como el beso y la fuga frente al colapso completo.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología celular Biología celular.
- La biofísica es la biofísica.
Sus antecedentes:
- La neurotransmisión se basa en la dinámica de las vesículas sinápticas dentro de las terminales presinápticas.
- El monitoreo preciso a escala nanométrica de estos movimientos de las vesículas ha sido un desafío significativo.
Objetivo del estudio:
- Desarrollar y aplicar un método para el seguimiento en tiempo real de alta precisión de vesículas sinápticas individuales.
- Para investigar la relación entre la posición de la vesícula, el movimiento y los eventos de fusión durante la neurotransmisión.
Principales métodos:
- Utilizó vesículas sinápticas cargadas de punto cuántico (Qdot) para el seguimiento tridimensional en tiempo real.
- Se logró una precisión a escala nanométrica (20-30 nm) en la localización de las vesículas.
- Se empleó el apagado azul de tripano de la fluorescencia Qdot para determinar eventos y modos de fusión.
Principales resultados:
- Las vesículas colocadas más cerca de los sitios de fusión exhibieron fusión anterior.
- El modo de fusión (beso y huida frente al colapso completo) dependía del movimiento previo de la vesícula.
- La fusión de beso y huida se produjo centralmente, mientras que la fusión de colapso completo se distribuyó más ampliamente.
Conclusiones:
- La proximidad de las vesículas a los sitios de fusión y la dinámica previa son determinantes críticos de la liberación de neurotransmisores.
- El estudio proporciona conocimientos espaciotemporales sin precedentes sobre los mecanismos de fusión de las vesículas sinápticas.
- Esta técnica ofrece una poderosa herramienta para el estudio de la función y disfunción sináptica.
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01:26Fusion of Secretory Vesicles with the Plasma Membrane
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
01:33Overview of Secretory Vesicles
Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
00:50Exocytosis
Exocytosis is a process that releases molecules outside the cell. Like other bulk transport mechanisms, exocytosis requires energy.
Exocytosis is the opposite of endocytosis, which brings molecules inside the cell. Sometimes, the released materials are signaling molecules. For example, neurons typically use exocytosis to release neurotransmitters. Cells also use exocytosis to insert proteins such as ion channels into their cell membranes, secrete proteins for use in the extracellular matrix, or...
Exocytosis is the opposite of endocytosis, which brings molecules inside the cell. Sometimes, the released materials are signaling molecules. For example, neurons typically use exocytosis to release neurotransmitters. Cells also use exocytosis to insert proteins such as ion channels into their cell membranes, secrete proteins for use in the extracellular matrix, or...
00:51Exocytosis
Exocytosis is used to release material from cells. Like other bulk transport mechanisms, exocytosis requires energy.
01:43SNAREs and Membrane Fusion
Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
01:26Chemical Synapses
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...