ACAP3 (ArfGAP with coiled-coil, ankyrin repeat and pleckstrin homology domains 3) belongs to the ACAP family of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). However, its specificity to Arf isoforms and physiological functions remain unclear. In the present study, we demonstrate that ACAP3 plays an important role in neurite outgrowth of mouse hippocampal neurons through its GAP activity specific to Arf6. In primary cultured mouse hippocampal neurons, knockdown of ACAP3 abrogated neurite outgrowth, which was rescued by ectopically expressed wild-type ACAP3, but not by its GAP activity-deficient mutant. Ectopically expressed ACAP3 in HEK (human embryonic kidney)-293T cells showed the GAP activity specific to Arf6. In support of this observation, the level of GTP-bound Arf6 was significantly increased by knockdown of ACAP3 in hippocampal neurons. In addition, knockdown and knockout of Arf6 in mouse hippocampal neurons suppressed neurite outgrowth. These results demonstrate that ACAP3 positively regulates neurite outgrowth through its GAP activity specific to Arf6. Furthermore, neurite outgrowth suppressed by ACAP3 knockdown was rescued by expression of a fast cycle mutant of Arf6 that spontaneously exchanges guanine nucleotides on Arf6, but not by that of wild-type, GTP- or GDP-locked mutant Arf6. Thus cycling between active and inactive forms of Arf6, which is precisely regulated by ACAP3 in concert with a guanine-nucleotide-exchange factor(s), seems to be required for neurite outgrowth of hippocampal neurons.
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September 2016
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Probing protein folding with ultrafast methods: these are explored in the review by Munoz and Cerminara in this issue (Volume 473, Issue 17, pages 2545–2559). Image kindly provided by Victor Munoz. - PDF Icon PDF LinkFront Matter
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Research Article|
August 30 2016
ACAP3 regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons
Yuki Miura;
Yuki Miura
1
*Department of Physiological Chemistry, Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan
†School of Integrative and Global Majors, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan
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Tsunaki Hongu;
Tsunaki Hongu
1
*Department of Physiological Chemistry, Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan
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Yohei Yamauchi;
Yohei Yamauchi
*Department of Physiological Chemistry, Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan
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Yuji Funakoshi;
Yuji Funakoshi
*Department of Physiological Chemistry, Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan
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Naohiro Katagiri;
Naohiro Katagiri
*Department of Physiological Chemistry, Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan
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Norihiko Ohbayashi;
Norihiko Ohbayashi
*Department of Physiological Chemistry, Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan
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Yasunori Kanaho
Yasunori Kanaho
2
*Department of Physiological Chemistry, Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan
2To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
March 02 2016
Revision Received:
June 10 2016
Accepted:
June 21 2016
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Biochem J (2016) 473 (17): 2591–2602.
Article history
Received:
March 02 2016
Revision Received:
June 10 2016
Accepted:
June 21 2016
Citation
Yuki Miura, Tsunaki Hongu, Yohei Yamauchi, Yuji Funakoshi, Naohiro Katagiri, Norihiko Ohbayashi, Yasunori Kanaho; ACAP3 regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons. Biochem J 1 September 2016; 473 (17): 2591–2602. doi: https://doi.org/10.1042/BCJ20160183
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