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EHD2 regulates plasma membrane integrity and downstream insulin receptor signalling events

Neuhaus, Mathis LU orcid ; Fryklund, Claes LU ; Taylor, Holly ; Borreguero-Muñoz, Andrea LU ; Kopietz, Franziska LU orcid ; Ardalani, Hamidreza LU ; Rogova, Oksana LU ; Stirrat, Laura ; Bremner, Shaun K and Spégel, Peter LU , et al. (2023) In Molecular Biology of the Cell 34(12).
Abstract

Adipocyte dysfunction is a crucial driver of insulin resistance and type 2 diabetes. We identified EH domain-containing protein 2 (EHD2) as one of the most highly upregulated genes at the early stage of adipose tissue expansion. EHD2 is a dynamin-related ATPase influencing several cellular processes, including membrane recycling, caveolae dynamics and lipid metabolism. Here, we investigated the role of EHD2 in adipocyte insulin signalling and glucose transport. Using C57BL6/N EHD2 knockout mice under short-term high-fat diet conditions and 3T3-L1 adipocytes we demonstrate that EHD2 deficiency is associated with deterioration of insulin signal transduction and impaired insulin-stimulated GLUT4 translocation. Furthermore, we show that... (More)

Adipocyte dysfunction is a crucial driver of insulin resistance and type 2 diabetes. We identified EH domain-containing protein 2 (EHD2) as one of the most highly upregulated genes at the early stage of adipose tissue expansion. EHD2 is a dynamin-related ATPase influencing several cellular processes, including membrane recycling, caveolae dynamics and lipid metabolism. Here, we investigated the role of EHD2 in adipocyte insulin signalling and glucose transport. Using C57BL6/N EHD2 knockout mice under short-term high-fat diet conditions and 3T3-L1 adipocytes we demonstrate that EHD2 deficiency is associated with deterioration of insulin signal transduction and impaired insulin-stimulated GLUT4 translocation. Furthermore, we show that lack of EHD2 is linked with altered plasma membrane lipid and protein composition, reduced insulin receptor expression, and diminished insulin-dependent SNARE protein complex formation. In conclusion, these data highlight the importance of EHD2 for the integrity of the plasma membrane milieu, insulin receptor stability, and downstream insulin receptor signalling events, involved in glucose uptake and ultimately underscore its role in insulin resistance and obesity.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Biology of the Cell
volume
34
issue
12
article number
ar124
publisher
American Society for Cell Biology
external identifiers
  • scopus:85175742345
  • pmid:37703099
ISSN
1939-4586
DOI
10.1091/mbc.E23-03-0078
language
English
LU publication?
yes
id
b25bb3b1-00bc-4587-b6fb-d74d99ffd2ce
date added to LUP
2023-10-25 21:34:36
date last changed
2024-04-25 03:00:25
@article{b25bb3b1-00bc-4587-b6fb-d74d99ffd2ce,
  abstract     = {{<p>Adipocyte dysfunction is a crucial driver of insulin resistance and type 2 diabetes. We identified EH domain-containing protein 2 (EHD2) as one of the most highly upregulated genes at the early stage of adipose tissue expansion. EHD2 is a dynamin-related ATPase influencing several cellular processes, including membrane recycling, caveolae dynamics and lipid metabolism. Here, we investigated the role of EHD2 in adipocyte insulin signalling and glucose transport. Using C57BL6/N EHD2 knockout mice under short-term high-fat diet conditions and 3T3-L1 adipocytes we demonstrate that EHD2 deficiency is associated with deterioration of insulin signal transduction and impaired insulin-stimulated GLUT4 translocation. Furthermore, we show that lack of EHD2 is linked with altered plasma membrane lipid and protein composition, reduced insulin receptor expression, and diminished insulin-dependent SNARE protein complex formation. In conclusion, these data highlight the importance of EHD2 for the integrity of the plasma membrane milieu, insulin receptor stability, and downstream insulin receptor signalling events, involved in glucose uptake and ultimately underscore its role in insulin resistance and obesity.</p>}},
  author       = {{Neuhaus, Mathis and Fryklund, Claes and Taylor, Holly and Borreguero-Muñoz, Andrea and Kopietz, Franziska and Ardalani, Hamidreza and Rogova, Oksana and Stirrat, Laura and Bremner, Shaun K and Spégel, Peter and Bryant, Nia J and Gould, Gwyn W and Stenkula, Karin G}},
  issn         = {{1939-4586}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{12}},
  publisher    = {{American Society for Cell Biology}},
  series       = {{Molecular Biology of the Cell}},
  title        = {{EHD2 regulates plasma membrane integrity and downstream insulin receptor signalling events}},
  url          = {{http://dx.doi.org/10.1091/mbc.E23-03-0078}},
  doi          = {{10.1091/mbc.E23-03-0078}},
  volume       = {{34}},
  year         = {{2023}},
}