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The brain-specific RasGEF very-KIND is required for normal dendritic growth in cerebellar granule cells and proper motor coordination
Very-KIND/Kndc1/KIAA1768 (v-KIND) is a brain-specific Ras guanine nucleotide exchange factor carrying two sets of the kinase non-catalytic C-lobe domain (KIND), and is predominantly expressed in cerebellar granule cells. Here, we report the impact of v-KIND deficiency on dendritic and synaptic growt...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338823/ https://www.ncbi.nlm.nih.gov/pubmed/28264072 http://dx.doi.org/10.1371/journal.pone.0173175 |
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author | Hayashi, Kanehiro Furuya, Asako Sakamaki, Yuriko Akagi, Takumi Shinoda, Yo Sadakata, Tetsushi Hashikawa, Tsutomu Shimizu, Kazuki Minami, Haruka Sano, Yoshitake Nakayama, Manabu Furuichi, Teiichi |
author_facet | Hayashi, Kanehiro Furuya, Asako Sakamaki, Yuriko Akagi, Takumi Shinoda, Yo Sadakata, Tetsushi Hashikawa, Tsutomu Shimizu, Kazuki Minami, Haruka Sano, Yoshitake Nakayama, Manabu Furuichi, Teiichi |
author_sort | Hayashi, Kanehiro |
collection | PubMed |
description | Very-KIND/Kndc1/KIAA1768 (v-KIND) is a brain-specific Ras guanine nucleotide exchange factor carrying two sets of the kinase non-catalytic C-lobe domain (KIND), and is predominantly expressed in cerebellar granule cells. Here, we report the impact of v-KIND deficiency on dendritic and synaptic growth in cerebellar granule cells in v-KIND knockout (KO) mice. Furthermore, we evaluate motor function in these animals. The gross anatomy of the cerebellum, including the cerebellar lobules, layered cerebellar cortex and densely-packed granule cell layer, in KO mice appeared normal, and was similar to wild-type (WT) mice. However, KO mice displayed an overgrowth of cerebellar granule cell dendrites, compared with WT mice, resulting in an increased number of dendrites, dendritic branches and terminals. Immunoreactivity for vGluT2 (a marker for excitatory presynapses of mossy fiber terminals) was increased in the cerebellar glomeruli of KO mice, compared with WT mice. The postsynaptic density around the terminals of mossy fibers was also increased in KO mice. Although there were no significant differences in locomotor ability between KO and WT animals in their home cages or in the open field, young adult KO mice had an increased grip strength and a tendency to exhibit better motor performance in balance-related tests compared with WT animals. Taken together, our results suggest that v-KIND is required for compact dendritic growth and proper excitatory synaptic connections in cerebellar granule cells, which are necessary for normal motor coordination and balance. |
format | Online Article Text |
id | pubmed-5338823 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-53388232017-03-10 The brain-specific RasGEF very-KIND is required for normal dendritic growth in cerebellar granule cells and proper motor coordination Hayashi, Kanehiro Furuya, Asako Sakamaki, Yuriko Akagi, Takumi Shinoda, Yo Sadakata, Tetsushi Hashikawa, Tsutomu Shimizu, Kazuki Minami, Haruka Sano, Yoshitake Nakayama, Manabu Furuichi, Teiichi PLoS One Research Article Very-KIND/Kndc1/KIAA1768 (v-KIND) is a brain-specific Ras guanine nucleotide exchange factor carrying two sets of the kinase non-catalytic C-lobe domain (KIND), and is predominantly expressed in cerebellar granule cells. Here, we report the impact of v-KIND deficiency on dendritic and synaptic growth in cerebellar granule cells in v-KIND knockout (KO) mice. Furthermore, we evaluate motor function in these animals. The gross anatomy of the cerebellum, including the cerebellar lobules, layered cerebellar cortex and densely-packed granule cell layer, in KO mice appeared normal, and was similar to wild-type (WT) mice. However, KO mice displayed an overgrowth of cerebellar granule cell dendrites, compared with WT mice, resulting in an increased number of dendrites, dendritic branches and terminals. Immunoreactivity for vGluT2 (a marker for excitatory presynapses of mossy fiber terminals) was increased in the cerebellar glomeruli of KO mice, compared with WT mice. The postsynaptic density around the terminals of mossy fibers was also increased in KO mice. Although there were no significant differences in locomotor ability between KO and WT animals in their home cages or in the open field, young adult KO mice had an increased grip strength and a tendency to exhibit better motor performance in balance-related tests compared with WT animals. Taken together, our results suggest that v-KIND is required for compact dendritic growth and proper excitatory synaptic connections in cerebellar granule cells, which are necessary for normal motor coordination and balance. Public Library of Science 2017-03-06 /pmc/articles/PMC5338823/ /pubmed/28264072 http://dx.doi.org/10.1371/journal.pone.0173175 Text en © 2017 Hayashi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Hayashi, Kanehiro Furuya, Asako Sakamaki, Yuriko Akagi, Takumi Shinoda, Yo Sadakata, Tetsushi Hashikawa, Tsutomu Shimizu, Kazuki Minami, Haruka Sano, Yoshitake Nakayama, Manabu Furuichi, Teiichi The brain-specific RasGEF very-KIND is required for normal dendritic growth in cerebellar granule cells and proper motor coordination |
title | The brain-specific RasGEF very-KIND is required for normal dendritic growth in cerebellar granule cells and proper motor coordination |
title_full | The brain-specific RasGEF very-KIND is required for normal dendritic growth in cerebellar granule cells and proper motor coordination |
title_fullStr | The brain-specific RasGEF very-KIND is required for normal dendritic growth in cerebellar granule cells and proper motor coordination |
title_full_unstemmed | The brain-specific RasGEF very-KIND is required for normal dendritic growth in cerebellar granule cells and proper motor coordination |
title_short | The brain-specific RasGEF very-KIND is required for normal dendritic growth in cerebellar granule cells and proper motor coordination |
title_sort | brain-specific rasgef very-kind is required for normal dendritic growth in cerebellar granule cells and proper motor coordination |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338823/ https://www.ncbi.nlm.nih.gov/pubmed/28264072 http://dx.doi.org/10.1371/journal.pone.0173175 |
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