Open AccessThe brain-specific RasGEF very-KIND is required for normal dendritic growth in cerebellar granule cells and proper motor coordination
Author(s) -
Hiromichi Kanehiro,
Asako Furuya,
Yuriko Sakamaki,
Tomonori Akagi,
Yo Shinoda,
Tetsushi Sadakata,
Tsutomu Hashikawa,
Kazuki Shimizu,
Haruka Minami,
Yoshitake Sano,
Manabu Nakayama,
Teiichi Furuichi
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0173175
Subject(s) - cerebellum , cerebellar cortex , motor coordination , excitatory postsynaptic potential , purkinje cell , granule cell , neuroscience , granule (geology) , knockout mouse , dendritic spine , biology , postsynaptic potential , chemistry , anatomy , microbiology and biotechnology , receptor , central nervous system , inhibitory postsynaptic potential , hippocampal formation , biochemistry , dentate gyrus , paleontology
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.