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...

Full description

Saved in:
Bibliographic Details
Main Authors: Yasunori Yamamoto, Toshiaki Sakisaka
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Autophagy Reports
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/27694127.2025.2513466
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850121111774167040
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