Palmitoylated small GTPase ARL15 is translocated within Golgi network during adipogenesis
The small GTPase ARF family member ARL15 gene locus is associated in population studies with increased risk of type 2 diabetes, lower adiponectin and higher fasting insulin levels. Previously, loss of ARL15 was shown to reduce insulin secretion in a human β-cell line and loss-of-function mutations a...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2021-12-01
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| Series: | Biology Open |
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| Online Access: | http://bio.biologists.org/content/10/12/bio058420 |
| _version_ | 1798032663544594432 |
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| author | Yixing Wu Ying Bai David G. McEwan Liz Bentley Dimitra Aravani Roger D. Cox |
| author_facet | Yixing Wu Ying Bai David G. McEwan Liz Bentley Dimitra Aravani Roger D. Cox |
| author_sort | Yixing Wu |
| collection | DOAJ |
| description | The small GTPase ARF family member ARL15 gene locus is associated in population studies with increased risk of type 2 diabetes, lower adiponectin and higher fasting insulin levels. Previously, loss of ARL15 was shown to reduce insulin secretion in a human β-cell line and loss-of-function mutations are found in some lipodystrophy patients. We set out to understand the role of ARL15 in adipogenesis and showed that endogenous ARL15 palmitoylated and localised in the Golgi of mouse liver. Adipocyte overexpression of palmitoylation-deficient ARL15 resulted in redistribution to the cytoplasm and a mild reduction in expression of some adipogenesis-related genes. Further investigation of the localisation of ARL15 during differentiation of a human white adipocyte cell line showed that ARL15 was predominantly co-localised with a marker of the cis face of Golgi at the preadipocyte stage and then translocated to other Golgi compartments after differentiation was induced. Finally, co-immunoprecipitation and mass spectrometry identified potential interacting partners of ARL15, including the ER-localised protein ARL6IP5. Together, these results suggest a palmitoylation dependent trafficking-related role of ARL15 as a regulator of adipocyte differentiation via ARL6IP5 interaction. This article has an associated First Person interview with the first author of the paper. |
| first_indexed | 2024-04-11T20:17:28Z |
| format | Article |
| id | doaj.art-e5a87e8d34b74befb9f2fc9a9ea03077 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-04-11T20:17:28Z |
| publishDate | 2021-12-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-e5a87e8d34b74befb9f2fc9a9ea030772022-12-22T04:04:55ZengThe Company of BiologistsBiology Open2046-63902021-12-01101210.1242/bio.058420058420Palmitoylated small GTPase ARL15 is translocated within Golgi network during adipogenesisYixing Wu0Ying Bai1David G. McEwan2Liz Bentley3Dimitra Aravani4Roger D. Cox5 Mammalian Genetics Unit, MRC Harwell Institute, Harwell Oxford, Oxfordshire, OX11 0RD, UK Mammalian Genetics Unit, MRC Harwell Institute, Harwell Oxford, Oxfordshire, OX11 0RD, UK Division of Cell Signalling & Immunology, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK Mammalian Genetics Unit, MRC Harwell Institute, Harwell Oxford, Oxfordshire, OX11 0RD, UK Mammalian Genetics Unit, MRC Harwell Institute, Harwell Oxford, Oxfordshire, OX11 0RD, UK Mammalian Genetics Unit, MRC Harwell Institute, Harwell Oxford, Oxfordshire, OX11 0RD, UK The small GTPase ARF family member ARL15 gene locus is associated in population studies with increased risk of type 2 diabetes, lower adiponectin and higher fasting insulin levels. Previously, loss of ARL15 was shown to reduce insulin secretion in a human β-cell line and loss-of-function mutations are found in some lipodystrophy patients. We set out to understand the role of ARL15 in adipogenesis and showed that endogenous ARL15 palmitoylated and localised in the Golgi of mouse liver. Adipocyte overexpression of palmitoylation-deficient ARL15 resulted in redistribution to the cytoplasm and a mild reduction in expression of some adipogenesis-related genes. Further investigation of the localisation of ARL15 during differentiation of a human white adipocyte cell line showed that ARL15 was predominantly co-localised with a marker of the cis face of Golgi at the preadipocyte stage and then translocated to other Golgi compartments after differentiation was induced. Finally, co-immunoprecipitation and mass spectrometry identified potential interacting partners of ARL15, including the ER-localised protein ARL6IP5. Together, these results suggest a palmitoylation dependent trafficking-related role of ARL15 as a regulator of adipocyte differentiation via ARL6IP5 interaction. This article has an associated First Person interview with the first author of the paper.http://bio.biologists.org/content/10/12/bio058420arl15adipogenesispalmitoylation |
| spellingShingle | Yixing Wu Ying Bai David G. McEwan Liz Bentley Dimitra Aravani Roger D. Cox Palmitoylated small GTPase ARL15 is translocated within Golgi network during adipogenesis Biology Open arl15 adipogenesis palmitoylation |
| title | Palmitoylated small GTPase ARL15 is translocated within Golgi network during adipogenesis |
| title_full | Palmitoylated small GTPase ARL15 is translocated within Golgi network during adipogenesis |
| title_fullStr | Palmitoylated small GTPase ARL15 is translocated within Golgi network during adipogenesis |
| title_full_unstemmed | Palmitoylated small GTPase ARL15 is translocated within Golgi network during adipogenesis |
| title_short | Palmitoylated small GTPase ARL15 is translocated within Golgi network during adipogenesis |
| title_sort | palmitoylated small gtpase arl15 is translocated within golgi network during adipogenesis |
| topic | arl15 adipogenesis palmitoylation |
| url | http://bio.biologists.org/content/10/12/bio058420 |
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