Mice lacking EFA6C/Psd2, a guanine nucleotide exchange factor for Arf6, exhibit lower Purkinje cell synaptic density but normal cerebellar motor functions

Shintaro Saegusa, Masahiro Fukaya, Wataru Kakegawa, Manabu Tanaka, Osamu Katsumata, Takeyuki Sugawara, Yoshinobu Hara, Makoto Itakura, Tadashi Okubo, Toshiya Sato, Michisuke Yuzaki, Hiroyuki Sakagami

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article numbere0216960
JournalPloS one
Volume14
Issue number5
DOIs
Publication statusPublished - 2019 May 1

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Guanine Nucleotide Exchange Factors
Purkinje Cells
Knockout Mice
Clustered Regularly Interspaced Short Palindromic Repeats
Cell Count
Cerebellar Cortex
Monomeric GTP-Binding Proteins
Fibers
mice
Synapses
Plasticity
Actins
cells
synapse
Dendritic Spines
Neuronal Plasticity
Electrons
cortex
Dendrites
Actin Cytoskeleton

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Mice lacking EFA6C/Psd2, a guanine nucleotide exchange factor for Arf6, exhibit lower Purkinje cell synaptic density but normal cerebellar motor functions. / Saegusa, Shintaro; Fukaya, Masahiro; Kakegawa, Wataru; Tanaka, Manabu; Katsumata, Osamu; Sugawara, Takeyuki; Hara, Yoshinobu; Itakura, Makoto; Okubo, Tadashi; Sato, Toshiya; Yuzaki, Michisuke; Sakagami, Hiroyuki.

In: PloS one, Vol. 14, No. 5, e0216960, 01.05.2019.

Research output: Contribution to journalArticle

Saegusa, Shintaro ; Fukaya, Masahiro ; Kakegawa, Wataru ; Tanaka, Manabu ; Katsumata, Osamu ; Sugawara, Takeyuki ; Hara, Yoshinobu ; Itakura, Makoto ; Okubo, Tadashi ; Sato, Toshiya ; Yuzaki, Michisuke ; Sakagami, Hiroyuki. / Mice lacking EFA6C/Psd2, a guanine nucleotide exchange factor for Arf6, exhibit lower Purkinje cell synaptic density but normal cerebellar motor functions. In: PloS one. 2019 ; Vol. 14, No. 5.
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