ADP ribosylation factor-like GTPase 6-interacting protein 5 (ARL6IP5): a prenylated Rab acceptor protein 1 (PRA1) family protein that shapes the ER membrane and regulates ER-phagy
The prenylated Rab acceptor protein 1 (PRA1) domain is a conserved domain encompassing four transmembrane domains (TMDs). ARL6IP5 (ADP ribosylation factor-like GTPase 6-interacting protein 5) is a member of the PRA1 family and interacts with the reticulon-homology domain (RHD)-containing proteins in...
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Taylor & Francis Group
2025-12-01
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| Series: | Autophagy Reports |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/27694127.2025.2513466 |
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| author | Yasunori Yamamoto Toshiaki Sakisaka |
| author_facet | Yasunori Yamamoto Toshiaki Sakisaka |
| author_sort | Yasunori Yamamoto |
| collection | DOAJ |
| description | The prenylated Rab acceptor protein 1 (PRA1) domain is a conserved domain encompassing four transmembrane domains (TMDs). ARL6IP5 (ADP ribosylation factor-like GTPase 6-interacting protein 5) is a member of the PRA1 family and interacts with the reticulon-homology domain (RHD)-containing proteins including ARL6IP1 (ADP ribosylation factor-like GTPase 6-interacting protein 1) and FAM134B. The RHD is a conserved domain encompassing two short hairpin TMDs and acts as a membrane-shaping unit for endoplasmic reticulum (ER) morphology and ER-phagy. However, the involvement of ARL6IP5 in ER morphology and ER-phagy remains unclear. We recently characterized ARL6IP5 as an ER membrane-shaping protein and found that ARL6IP5 constricts the ER membrane in a manner similar to ARL6IP1, possibly via short hairpin configuration of the TMDs in the PRA1 domain. ARL6IP5 also plays a redundant role with ARL6IP1 in shaping the ER membrane. Importantly, depletion of ARL6IP5 impaired FAM134B-meadited ER-phagy, which is reminiscent of ARL6IP1 depletion. These results suggested that ARL6IP5 acts as an ER membrane-shaping protein that regulates ER-phagy, underscoring the importance of the PRA1 domain. Although ARL6IP5 and ARL6IP1 are confusable protein names and seem to have similar roles in ER-phagy, we clarify in this punctum that they are distinct classes of ER membrane-shaping proteins. |
| format | Article |
| id | doaj-art-6c1f7dea74f9431fa94d45d31dfcacee |
| institution | OA Journals |
| issn | 2769-4127 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autophagy Reports |
| spelling | doaj-art-6c1f7dea74f9431fa94d45d31dfcacee2025-08-20T02:35:11ZengTaylor & Francis GroupAutophagy Reports2769-41272025-12-014110.1080/27694127.2025.2513466ADP ribosylation factor-like GTPase 6-interacting protein 5 (ARL6IP5): a prenylated Rab acceptor protein 1 (PRA1) family protein that shapes the ER membrane and regulates ER-phagyYasunori Yamamoto0Toshiaki Sakisaka1Division of Membrane Dynamics, Department of Physiology and Cell Biology, Kobe University School of Medicine, Kobe, JapanDivision of Membrane Dynamics, Department of Physiology and Cell Biology, Kobe University School of Medicine, Kobe, JapanThe prenylated Rab acceptor protein 1 (PRA1) domain is a conserved domain encompassing four transmembrane domains (TMDs). ARL6IP5 (ADP ribosylation factor-like GTPase 6-interacting protein 5) is a member of the PRA1 family and interacts with the reticulon-homology domain (RHD)-containing proteins including ARL6IP1 (ADP ribosylation factor-like GTPase 6-interacting protein 1) and FAM134B. The RHD is a conserved domain encompassing two short hairpin TMDs and acts as a membrane-shaping unit for endoplasmic reticulum (ER) morphology and ER-phagy. However, the involvement of ARL6IP5 in ER morphology and ER-phagy remains unclear. We recently characterized ARL6IP5 as an ER membrane-shaping protein and found that ARL6IP5 constricts the ER membrane in a manner similar to ARL6IP1, possibly via short hairpin configuration of the TMDs in the PRA1 domain. ARL6IP5 also plays a redundant role with ARL6IP1 in shaping the ER membrane. Importantly, depletion of ARL6IP5 impaired FAM134B-meadited ER-phagy, which is reminiscent of ARL6IP1 depletion. These results suggested that ARL6IP5 acts as an ER membrane-shaping protein that regulates ER-phagy, underscoring the importance of the PRA1 domain. Although ARL6IP5 and ARL6IP1 are confusable protein names and seem to have similar roles in ER-phagy, we clarify in this punctum that they are distinct classes of ER membrane-shaping proteins.https://www.tandfonline.com/doi/10.1080/27694127.2025.2513466Endoplasmic reticulumER-phagyprenylated Rab acceptor protein 1 domainreticulon-homology domainARL6IP5ARL6IP1 |
| spellingShingle | Yasunori Yamamoto Toshiaki Sakisaka ADP ribosylation factor-like GTPase 6-interacting protein 5 (ARL6IP5): a prenylated Rab acceptor protein 1 (PRA1) family protein that shapes the ER membrane and regulates ER-phagy Autophagy Reports Endoplasmic reticulum ER-phagy prenylated Rab acceptor protein 1 domain reticulon-homology domain ARL6IP5 ARL6IP1 |
| title | ADP ribosylation factor-like GTPase 6-interacting protein 5 (ARL6IP5): a prenylated Rab acceptor protein 1 (PRA1) family protein that shapes the ER membrane and regulates ER-phagy |
| title_full | ADP ribosylation factor-like GTPase 6-interacting protein 5 (ARL6IP5): a prenylated Rab acceptor protein 1 (PRA1) family protein that shapes the ER membrane and regulates ER-phagy |
| title_fullStr | ADP ribosylation factor-like GTPase 6-interacting protein 5 (ARL6IP5): a prenylated Rab acceptor protein 1 (PRA1) family protein that shapes the ER membrane and regulates ER-phagy |
| title_full_unstemmed | ADP ribosylation factor-like GTPase 6-interacting protein 5 (ARL6IP5): a prenylated Rab acceptor protein 1 (PRA1) family protein that shapes the ER membrane and regulates ER-phagy |
| title_short | ADP ribosylation factor-like GTPase 6-interacting protein 5 (ARL6IP5): a prenylated Rab acceptor protein 1 (PRA1) family protein that shapes the ER membrane and regulates ER-phagy |
| title_sort | adp ribosylation factor like gtpase 6 interacting protein 5 arl6ip5 a prenylated rab acceptor protein 1 pra1 family protein that shapes the er membrane and regulates er phagy |
| topic | Endoplasmic reticulum ER-phagy prenylated Rab acceptor protein 1 domain reticulon-homology domain ARL6IP5 ARL6IP1 |
| url | https://www.tandfonline.com/doi/10.1080/27694127.2025.2513466 |
| work_keys_str_mv | AT yasunoriyamamoto adpribosylationfactorlikegtpase6interactingprotein5arl6ip5aprenylatedrabacceptorprotein1pra1familyproteinthatshapestheermembraneandregulateserphagy AT toshiakisakisaka adpribosylationfactorlikegtpase6interactingprotein5arl6ip5aprenylatedrabacceptorprotein1pra1familyproteinthatshapestheermembraneandregulateserphagy |