The brain-specific RasGEF very-KIND is required for normal dendritic growth in cerebellar granule cells and proper motor coordination
| Autor: | Teiichi Furuichi, Asako Furuya, Kazuki Shimizu, Tetsushi Sadakata, Tsutomu Hashikawa, Manabu Nakayama, Kanehiro Hayashi, Haruka Minami, Takumi Akagi, Yoshitake Sano, Yuriko Sakamaki, Yo Shinoda |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cerebellum Physiology lcsh:Medicine Nervous System Mice 0302 clinical medicine Animal Cells Medicine and Health Sciences Guanine Nucleotide Exchange Factors lcsh:Science Animal Management Mice Knockout Neurons Mammals Cerebral Cortex Multidisciplinary Chemistry Granule (cell biology) Brain Agriculture Immunohistochemistry Motor coordination Cell biology Electrophysiology Golgi Cells medicine.anatomical_structure Organ Specificity Cerebellar cortex Vertebrates Excitatory postsynaptic potential Guanine nucleotide exchange factor Cellular Types Anatomy Research Article Neurophysiology Nerve Tissue Proteins Research and Analysis Methods Rodents 03 medical and health sciences medicine Animals Immunohistochemistry Techniques Animal Performance Granule Cells lcsh:R Organisms Excitatory Postsynaptic Potentials Biology and Life Sciences Dendrites Cell Biology Neuronal Dendrites Granule cell Axons Histochemistry and Cytochemistry Techniques 030104 developmental biology Cellular Neuroscience Synapses Amniotes Immunologic Techniques lcsh:Q Postsynaptic density Biomarkers Psychomotor Performance 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 3, p e0173175 (2017) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0173175 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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