Mice lacking EFA6C/Psd2, a guanine nucleotide exchange factor for Arf6, exhibit lower Purkinje cell synaptic density but normal cerebellar motor functions Article Swipe
Shintaro Saegusa
,
Masahiro Fukaya
,
Wataru Kakegawa
,
Manabu Tanaka
,
Osamu Katsumata
,
Takeyuki Sugawara
,
Yoshinobu Hara
,
Makoto Itakura
,
Tadashi Okubo
,
Toshiya Sato
,
Michisuke Yuzaki
,
Hiroyuki Sakagami
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pone.0216960
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pone.0216960
ADP ribosylation factor 6 (Arf6) is a small GTPase that regulates various neuronal events including formation of the axon, dendrites and dendritic spines, and synaptic plasticity through actin cytoskeleton remodeling and endosomal trafficking. EFA6C, also known as Psd2, is a guanine nucleotide exchange factor for Arf6 that is preferentially expressed in the cerebellar cortex of adult mice, particularly in Purkinje cells. However, the roles of EFA6C in cerebellar development and functions remain unknown. In this study, we generated global EFA6C knockout (KO) mice using the CRISPR/Cas9 system and investigated their cerebellar phenotypes by histological and behavioral analyses. Histological analyses revealed that EFA6C KO mice exhibited normal gross anatomy of the cerebellar cortex, in terms of the thickness and cellularity of each layer, morphology of Purkinje cells, and distribution patterns of parallel fibers, climbing fibers, and inhibitory synapses. Electron microscopic observation of the cerebellar molecular layer revealed that the density of asymmetric synapses of Purkinje cells was significantly lower in EFA6C KO mice compared with wild-type control mice. However, behavioral analyses using accelerating rotarod and horizontal optokinetic response tests failed to detect any differences in motor coordination, learning or adaptation between the control and EFA6C KO mice. These results suggest that EFA6C plays ancillary roles in cerebellar development and motor functions.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1371/journal.pone.0216960
- OA Status
- gold
- Cited By
- 3
- References
- 58
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2946277881
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- OpenAlex ID
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https://openalex.org/W2946277881Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1371/journal.pone.0216960Digital Object Identifier
- Title
-
Mice lacking EFA6C/Psd2, a guanine nucleotide exchange factor for Arf6, exhibit lower Purkinje cell synaptic density but normal cerebellar motor functionsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2019Year of publication
- Publication date
-
2019-05-16Full publication date if available
- Authors
-
Shintaro Saegusa, Masahiro Fukaya, Wataru Kakegawa, Manabu Tanaka, Osamu Katsumata, Takeyuki Sugawara, Yoshinobu Hara, Makoto Itakura, Tadashi Okubo, Toshiya Sato, Michisuke Yuzaki, Hiroyuki SakagamiList of authors in order
- Landing page
-
https://doi.org/10.1371/journal.pone.0216960Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1371/journal.pone.0216960Direct OA link when available
- Concepts
-
Cerebellar cortex, Dendritic spine, Purkinje cell, Cerebellum, Biology, Neuroscience, Climbing fiber, Knockout mouse, Guanine nucleotide exchange factor, Synapse, Motor coordination, Parallel fiber, Cell biology, GTPase, Biochemistry, Receptor, Hippocampal formationTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
3Total citation count in OpenAlex
- Citations by year (recent)
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2025: 1, 2024: 1, 2020: 1Per-year citation counts (last 5 years)
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58Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| referenced_works | https://openalex.org/W2068358300, https://openalex.org/W1964252660, https://openalex.org/W2127432085, https://openalex.org/W2103820041, https://openalex.org/W2046320033, https://openalex.org/W2493283524, https://openalex.org/W2162159318, https://openalex.org/W1993240989, https://openalex.org/W1974330164, https://openalex.org/W1964934349, https://openalex.org/W2124232966, https://openalex.org/W2047287933, https://openalex.org/W2044911441, https://openalex.org/W2231550233, https://openalex.org/W2046496537, https://openalex.org/W2053204504, https://openalex.org/W2162808713, https://openalex.org/W1946623472, https://openalex.org/W2089111454, https://openalex.org/W1972675549, https://openalex.org/W2083699120, https://openalex.org/W2016864095, https://openalex.org/W2064942214, https://openalex.org/W2111911623, https://openalex.org/W2011280723, https://openalex.org/W2098836340, https://openalex.org/W2036755668, https://openalex.org/W2953045849, https://openalex.org/W2408921101, https://openalex.org/W2625862705, https://openalex.org/W2079668152, https://openalex.org/W1559266775, https://openalex.org/W2054545874, https://openalex.org/W1996302022, https://openalex.org/W1804341529, https://openalex.org/W2889251628, https://openalex.org/W2738516258, https://openalex.org/W4293416615, https://openalex.org/W2112227347, https://openalex.org/W1984882298, https://openalex.org/W1992780981, https://openalex.org/W2904862960, https://openalex.org/W1993087061, https://openalex.org/W2074042976, https://openalex.org/W2156625231, https://openalex.org/W2080120821, https://openalex.org/W2120954774, https://openalex.org/W2160635048, https://openalex.org/W1970263992, https://openalex.org/W2121405440, https://openalex.org/W2046826693, https://openalex.org/W1992908125, https://openalex.org/W2128167753, https://openalex.org/W2006810449, https://openalex.org/W2327675986, https://openalex.org/W3096511464, https://openalex.org/W1978307370, https://openalex.org/W2361186928 |
| referenced_works_count | 58 |
| abstract_inverted_index.6 | 3 |
| abstract_inverted_index.a | 6, 39 |
| abstract_inverted_index.In | 73 |
| abstract_inverted_index.KO | 102, 160, 194 |
| abstract_inverted_index.as | 36 |
| abstract_inverted_index.by | 92 |
| abstract_inverted_index.in | 50, 58, 66, 112, 158, 183, 204 |
| abstract_inverted_index.is | 5, 38, 47 |
| abstract_inverted_index.of | 16, 54, 64, 108, 114, 119, 123, 129, 140, 149, 152 |
| abstract_inverted_index.or | 187 |
| abstract_inverted_index.to | 179 |
| abstract_inverted_index.we | 76 |
| abstract_inverted_index.ADP | 0 |
| abstract_inverted_index.and | 20, 23, 30, 69, 87, 94, 117, 126, 134, 173, 192, 207 |
| abstract_inverted_index.any | 181 |
| abstract_inverted_index.for | 44 |
| abstract_inverted_index.the | 17, 51, 62, 84, 109, 115, 141, 147, 190 |
| abstract_inverted_index.was | 155 |
| abstract_inverted_index.(KO) | 81 |
| abstract_inverted_index.Arf6 | 45 |
| abstract_inverted_index.also | 34 |
| abstract_inverted_index.each | 120 |
| abstract_inverted_index.mice | 82, 103, 161 |
| abstract_inverted_index.that | 9, 46, 100, 146, 199 |
| abstract_inverted_index.this | 74 |
| abstract_inverted_index.with | 163 |
| abstract_inverted_index.EFA6C | 65, 79, 101, 159, 193, 200 |
| abstract_inverted_index.Psd2, | 37 |
| abstract_inverted_index.These | 196 |
| abstract_inverted_index.actin | 27 |
| abstract_inverted_index.adult | 55 |
| abstract_inverted_index.axon, | 18 |
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| abstract_inverted_index.gross | 106 |
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| abstract_inverted_index.mice, | 56 |
| abstract_inverted_index.mice. | 166, 195 |
| abstract_inverted_index.motor | 184, 208 |
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| abstract_inverted_index.roles | 63, 203 |
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| abstract_inverted_index.their | 89 |
| abstract_inverted_index.using | 83, 170 |
| abstract_inverted_index.(Arf6) | 4 |
| abstract_inverted_index.EFA6C, | 33 |
| abstract_inverted_index.GTPase | 8 |
| abstract_inverted_index.cells, | 125 |
| abstract_inverted_index.cells. | 60 |
| abstract_inverted_index.cortex | 53 |
| abstract_inverted_index.detect | 180 |
| abstract_inverted_index.events | 13 |
| abstract_inverted_index.factor | 2, 43 |
| abstract_inverted_index.failed | 178 |
| abstract_inverted_index.global | 78 |
| abstract_inverted_index.layer, | 121 |
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| abstract_inverted_index.remain | 71 |
| abstract_inverted_index.study, | 75 |
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| abstract_inverted_index.control | 165, 191 |
| abstract_inverted_index.cortex, | 111 |
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| abstract_inverted_index.fibers, | 131, 133 |
| abstract_inverted_index.guanine | 40 |
| abstract_inverted_index.results | 197 |
| abstract_inverted_index.rotarod | 172 |
| abstract_inverted_index.spines, | 22 |
| abstract_inverted_index.suggest | 198 |
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| abstract_inverted_index.various | 11 |
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| abstract_inverted_index.However, | 61, 167 |
| abstract_inverted_index.Purkinje | 59, 124, 153 |
| abstract_inverted_index.analyses | 98, 169 |
| abstract_inverted_index.climbing | 132 |
| abstract_inverted_index.compared | 162 |
| abstract_inverted_index.exchange | 42 |
| abstract_inverted_index.knockout | 80 |
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| abstract_inverted_index.patterns | 128 |
| abstract_inverted_index.response | 176 |
| abstract_inverted_index.revealed | 99, 145 |
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| abstract_inverted_index.analyses. | 96 |
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| abstract_inverted_index.dendritic | 21 |
| abstract_inverted_index.endosomal | 31 |
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| abstract_inverted_index.adaptation | 188 |
| abstract_inverted_index.asymmetric | 150 |
| abstract_inverted_index.behavioral | 95, 168 |
| abstract_inverted_index.cerebellar | 52, 67, 90, 110, 142, 205 |
| abstract_inverted_index.functions. | 209 |
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| abstract_inverted_index.remodeling | 29 |
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| abstract_inverted_index.histological | 93 |
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| corresponding_author_ids | https://openalex.org/A5086842796, https://openalex.org/A5068311071, https://openalex.org/A5015389182, https://openalex.org/A5018695200, https://openalex.org/A5045135387, https://openalex.org/A5037533574, https://openalex.org/A5103198580, https://openalex.org/A5027707370, https://openalex.org/A5077366980, https://openalex.org/A5089568275, https://openalex.org/A5076281672, https://openalex.org/A5057638487 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 12 |
| corresponding_institution_ids | https://openalex.org/I203951103, https://openalex.org/I64189623 |
| citation_normalized_percentile.value | 0.43679935 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |