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Int. J. Mol. Sci. 2017, 18(11), 2281; https://doi.org/10.3390/ijms18112281

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

1
Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, 28040 Madrid, Spain
2
Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
3
FOR 923, Institut für Pharmakologie und Toxikologie, Technische Universität München, Biedersteiner Str. 29, 80802 Munich, Germany
*
Author to whom correspondence should be addressed.
Received: 28 September 2017 / Revised: 23 October 2017 / Accepted: 25 October 2017 / Published: 30 October 2017
(This article belongs to the Special Issue cGMP-Signalling in Cells: Molecular and Functional Features)
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Abstract

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. View Full-Text
Keywords: cerebellar granule cells; cGKI; cGKII; synaptic vesicle recycling; FM1-43; KT5823; VGluT-pH cerebellar granule cells; cGKI; cGKII; synaptic vesicle recycling; FM1-43; KT5823; VGluT-pH
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Collado-Alsina, A.; Hofmann, F.; Sánchez-Prieto, J.; Torres, M. Altered Synaptic Membrane Retrieval after Strong Stimulation of Cerebellar Granule Neurons in Cyclic GMP-Dependent Protein Kinase II (cGKII) Knockout Mice. Int. J. Mol. Sci. 2017, 18, 2281.

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