ARNO is recruited by the neuronal adaptor FE65 to potentiate ARF6-mediated neurite outgrowth
ADP-ribosylation factor 6 (ARF6) is a small GTPase that has a variety of neuronal functions including stimulating neurite outgrowth, a crucial process for the establishment and maintenance of neural connectivity. As impaired and atrophic neurites are often observed in various brain injuries and neur...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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The Royal Society
2022-09-01
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| Series: | Open Biology |
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| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsob.220071 |
| _version_ | 1797840317279371264 |
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| author | Yuqi Zhai Wai Wa Ray Chan Wen Li Kwok-Fai Lau |
| author_facet | Yuqi Zhai Wai Wa Ray Chan Wen Li Kwok-Fai Lau |
| author_sort | Yuqi Zhai |
| collection | DOAJ |
| description | ADP-ribosylation factor 6 (ARF6) is a small GTPase that has a variety of neuronal functions including stimulating neurite outgrowth, a crucial process for the establishment and maintenance of neural connectivity. As impaired and atrophic neurites are often observed in various brain injuries and neurological diseases, understanding the intrinsic pathways that stimulate neurite outgrowth may provide insights into developing strategies to trigger the reconnection of injured neurons. The neuronal adaptor FE65 has been shown to interact with ARF6 and potentiate ARF6-mediated neurite outgrowth. However, the precise mechanism that FE65 activates ARF6 remains unclear, as FE65 does not possess a guanine nucleotide exchange factor (GEF) domain/function. Here, we show that FE65 interacts with the ARF6 GEF, namely the ARF nucleotide-binding site opener (ARNO). Moreover, a complex consisting of ARNO, ARF6 and FE65 is detected. Notably, FE65 potentiates the stimulatory effect of ARNO on ARF6-mediated neurite outgrowth, and the effect of FE65 is abrogated by an FE65 mutation that disrupts FE65–ARNO interaction. Additionally, the intramolecular interaction for mediating the autoinhibited conformation of ARNO is attenuated by FE65. Moreover, FE65 potentiates the effects of wild-type ARNO, but not the monomeric mutant, suggesting an association between FE65 and ARNO dimerization. Collectively, we demonstrate that FE65 binds to and activates ARNO and, consequently, potentiates ARF6-mediated neurite outgrowth. |
| first_indexed | 2024-04-09T16:12:58Z |
| format | Article |
| id | doaj.art-fea1850cdd1a4b9d8a32081ee7b2b077 |
| institution | Directory Open Access Journal |
| issn | 2046-2441 |
| language | English |
| last_indexed | 2024-04-09T16:12:58Z |
| publishDate | 2022-09-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Open Biology |
| spelling | doaj.art-fea1850cdd1a4b9d8a32081ee7b2b0772023-04-24T09:14:29ZengThe Royal SocietyOpen Biology2046-24412022-09-0112910.1098/rsob.220071ARNO is recruited by the neuronal adaptor FE65 to potentiate ARF6-mediated neurite outgrowthYuqi Zhai0Wai Wa Ray Chan1Wen Li2Kwok-Fai Lau3School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong KongSchool of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong KongSchool of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong KongSchool of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong KongADP-ribosylation factor 6 (ARF6) is a small GTPase that has a variety of neuronal functions including stimulating neurite outgrowth, a crucial process for the establishment and maintenance of neural connectivity. As impaired and atrophic neurites are often observed in various brain injuries and neurological diseases, understanding the intrinsic pathways that stimulate neurite outgrowth may provide insights into developing strategies to trigger the reconnection of injured neurons. The neuronal adaptor FE65 has been shown to interact with ARF6 and potentiate ARF6-mediated neurite outgrowth. However, the precise mechanism that FE65 activates ARF6 remains unclear, as FE65 does not possess a guanine nucleotide exchange factor (GEF) domain/function. Here, we show that FE65 interacts with the ARF6 GEF, namely the ARF nucleotide-binding site opener (ARNO). Moreover, a complex consisting of ARNO, ARF6 and FE65 is detected. Notably, FE65 potentiates the stimulatory effect of ARNO on ARF6-mediated neurite outgrowth, and the effect of FE65 is abrogated by an FE65 mutation that disrupts FE65–ARNO interaction. Additionally, the intramolecular interaction for mediating the autoinhibited conformation of ARNO is attenuated by FE65. Moreover, FE65 potentiates the effects of wild-type ARNO, but not the monomeric mutant, suggesting an association between FE65 and ARNO dimerization. Collectively, we demonstrate that FE65 binds to and activates ARNO and, consequently, potentiates ARF6-mediated neurite outgrowth.https://royalsocietypublishing.org/doi/10.1098/rsob.220071ADP ribosylation factor 6amyloid β a4 precursor protein-binding family b member 1ARF nucleotide-binding site openerneurite outgrowth |
| spellingShingle | Yuqi Zhai Wai Wa Ray Chan Wen Li Kwok-Fai Lau ARNO is recruited by the neuronal adaptor FE65 to potentiate ARF6-mediated neurite outgrowth Open Biology ADP ribosylation factor 6 amyloid β a4 precursor protein-binding family b member 1 ARF nucleotide-binding site opener neurite outgrowth |
| title | ARNO is recruited by the neuronal adaptor FE65 to potentiate ARF6-mediated neurite outgrowth |
| title_full | ARNO is recruited by the neuronal adaptor FE65 to potentiate ARF6-mediated neurite outgrowth |
| title_fullStr | ARNO is recruited by the neuronal adaptor FE65 to potentiate ARF6-mediated neurite outgrowth |
| title_full_unstemmed | ARNO is recruited by the neuronal adaptor FE65 to potentiate ARF6-mediated neurite outgrowth |
| title_short | ARNO is recruited by the neuronal adaptor FE65 to potentiate ARF6-mediated neurite outgrowth |
| title_sort | arno is recruited by the neuronal adaptor fe65 to potentiate arf6 mediated neurite outgrowth |
| topic | ADP ribosylation factor 6 amyloid β a4 precursor protein-binding family b member 1 ARF nucleotide-binding site opener neurite outgrowth |
| url | https://royalsocietypublishing.org/doi/10.1098/rsob.220071 |
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