Altered Synaptic Membrane Retrieval after Strong Stimulation of Cerebellar Granule Neurons in Cyclic GMP-Dependent Protein Kinase II (cGKII) Knockout Mice

The nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (cGK) signaling pathway regulates the clustering and the recruitment of proteins and vesicles to the synapse, thereby adjusting the exoendocytic cycle to the intensity of activity. Accordingly, this pathway can...

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Detalles Bibliográficos
Autores: Collado Alsina, Andrea, Hofmann, Franz, Sánchez-Prieto Borja, José, Torres Molina, Magdalena Isabel
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/19143
Acceso en línea:https://hdl.handle.net/20.500.14352/19143
Access Level:acceso abierto
Palabra clave:cerebellar granule cells
cGKI
cGKII
synaptic vesicle recycling
FM1-43
KT5823
VGluT-pH
Animales de laboratorio
Microbiología (Veterinaria)
3109.05 Microbiología
Descripción
Sumario:The nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (cGK) signaling pathway regulates the clustering and the recruitment of proteins and vesicles to the synapse, thereby adjusting the exoendocytic cycle to the intensity of activity. Accordingly, this pathway can accelerate endocytosis following large-scale exocytosis, and pre-synaptic cGK type II (cGKII) plays a major role in this process, controlling the homeostatic balance of vesicle exocytosis and endocytosis. We have studied synaptic vesicle recycling in cerebellar granule cells from mice lacking cGKII under strong and sustained stimulation, combining imaging techniques and ultrastructural analyses. The ultrastructure of synapses in the adult mouse cerebellar cortex was also examined in these animals. The lack of cGKII provokes structural changes to synapses in cultured cells and in the cerebellar cortex. Moreover, endocytosis is slowed down in a subset of boutons in these cells when they are stimulated strongly. In addition, from the results obtained with the selective inhibitor of cGKs, KT5823, it can be concluded that cGKI also regulates some aspects of vesicle cycling. Overall, these results confirm the importance of the cGMP pathway in the regulation of vesicle cycling following strong stimulation of cerebellar granule cells.