Publication: Regulación del ciclo vesicular sináptico por las quinasas dependientes de GMPc en neuronas grabulares de cerebelo
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2016-07-04
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Universidad Complutense de Madrid
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Abstract
La comunicación entre las neuronas ocurre en regiones anatómicamente identificables denominadas sinapsis. Existen dos tipos de transmisión sináptica, las sinapsis químicas y las eléctricas, aunque predominan las sinapsis químicas. En este tipo de sinapsis, la comunicación neuronal ocurre en zonas especializadas de los axones, denominados terminales sinápticos, los cuales almacenan en su interior pequeñas vesículas que contienen un neurotransmisor. Ante la llegada de un potencial de acción al terminal presináptico, el flujo de calcio, generado a través de la apertura de canales de calcio voltaje-dependientes, provoca la fusión de las vesículas con la membrana del terminal presináptico, y la liberación del neurotransmisor a la hendidura sináptica. La fusión vesicular tiene lugar en regiones de membrana del terminal presináptico, molecularmente especializadas para dicho evento exocitótico, denominadas Zonas Activas. Este neurotransmisor liberado difunde por la hendidura sináptica y se une a receptores específicos ubicados en la membrana de la neurona postsináptica, propagándose así el impulso nervioso. Tras este evento exocitótico, que implica la fusión de multitud de vesículas, es necesario un proceso de endocitosis, que ocurre en las zonas perisinápticas, y que está encargado de recuperar las fracciones de membrana que formaban las vesículas sinápticas, con dos objetivos: 1. Impedir el aumento de la superficie de la zona activa, lo cual llevaría a su desestructuración, y 2. La formación de nuevas vesículas que se rellenen de neurotransmisor y puedan prepararse para una nueva ronda de exocitosis. La endocitosis que sigue a un estímulo moderado, está mediada por clatrina y recicla vesículas independientes preparadas para el rellenado con neurotransmisor. Tras estímulos intensos que provocan exocitosis de múltiples vesículas, la retirada de membrana ocurre a través de otro mecanismo más lento y menos eficaz, denominado endocitosis en masa, el cual recicla grandes fragmentos de membrana y acumula estructuras endosomales en el interior del terminal, los cuales no siempre rinden vesículas funcionales inmediatamente...
Communication between neurons takes place in anatomically recognizable regions called synapses. There are two types of synaptic transmission, chemical and electrical synapses, although chemical synapses are the ones that predominate. At this kind of synapses, interneuronal communication occurs at specialized regions of the axon, called synaptic terminals, structures that contain small vesicles filled with neurotransmitter. Upon the arrival of an action potential to the synaptic terminal, the calcium influx, which it́s generated through the opening of voltage-dependent calcium channels, induces the fusion of the small synaptic vesicles with the plasmatic membrane, and the release of the neurotransmitter to the synaptic cleft. This group of events, that includes vesicle fusion, takes place at specialized regions of the synaptic terminal, named Actives Zones. The neurotransmitter that has been released, binds to its specific receptors at the post synaptic element, spreading the nerve impulse. After the exocytotic event, that involves multi vesicular fusion, it́s required an endocytic process, that takes place at perisynaptic regions, with a main objective: the recovery of membrane fractions that formed synaptic vesicles, with two main purposes: 1. The prevention of the increase in the surface of the active zone, an event that will lead to the loss of its structure. 2. The formation of new vesicles to be filled with neurotransmitter, so they can be prepared to a new exocytotic event. The endocytosis process that follows middle stimulation, it́s mediated by a protein named clathrin, and recycles independent vesicles ready to be refilled with neurotransmitter. Stronger stimulus, which induces the fusion of a large number of vesicles, leads to a slower and less efficient endocytotic mechanism, named bulk endocytosis. This kind of endocytosis accumulated endosomal structures inside the synaptic terminal, endosomes that not always render new functional vesicles...
Communication between neurons takes place in anatomically recognizable regions called synapses. There are two types of synaptic transmission, chemical and electrical synapses, although chemical synapses are the ones that predominate. At this kind of synapses, interneuronal communication occurs at specialized regions of the axon, called synaptic terminals, structures that contain small vesicles filled with neurotransmitter. Upon the arrival of an action potential to the synaptic terminal, the calcium influx, which it́s generated through the opening of voltage-dependent calcium channels, induces the fusion of the small synaptic vesicles with the plasmatic membrane, and the release of the neurotransmitter to the synaptic cleft. This group of events, that includes vesicle fusion, takes place at specialized regions of the synaptic terminal, named Actives Zones. The neurotransmitter that has been released, binds to its specific receptors at the post synaptic element, spreading the nerve impulse. After the exocytotic event, that involves multi vesicular fusion, it́s required an endocytic process, that takes place at perisynaptic regions, with a main objective: the recovery of membrane fractions that formed synaptic vesicles, with two main purposes: 1. The prevention of the increase in the surface of the active zone, an event that will lead to the loss of its structure. 2. The formation of new vesicles to be filled with neurotransmitter, so they can be prepared to a new exocytotic event. The endocytosis process that follows middle stimulation, it́s mediated by a protein named clathrin, and recycles independent vesicles ready to be refilled with neurotransmitter. Stronger stimulus, which induces the fusion of a large number of vesicles, leads to a slower and less efficient endocytotic mechanism, named bulk endocytosis. This kind of endocytosis accumulated endosomal structures inside the synaptic terminal, endosomes that not always render new functional vesicles...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Veterinaria, Sección Departamental de Bioquímica y Biología Molecular I, leída el 14/12/2015