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EHD2-mediated restriction of caveolar dynamics regulates cellular fatty acid uptake

Eps15-homology domain containing protein 2 (EHD2) is a dynamin-related ATPase located at the neck of caveolae, but its physiological function has remained unclear. Here, we found that global genetic ablation of EHD2 in mice leads to increased lipid droplet size in fat tissue. This organismic phenoty...

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Main Authors: Matthäus, Claudia (Author) , Lahmann, Ines (Author) , Kunz, Séverine (Author) , Jonas, Wenke (Author) , Melo, Arthur Alves (Author) , Lehmann, Martin (Author) , Larsson, Elin (Author) , Lundmark, Richard (Author) , Kern, Matthias (Author) , Blüher, Matthias (Author) , Olschowski, Hannah (Author) , Kompa, Julian (Author) , Brügger, Britta (Author) , Müller, Dominik N. (Author) , Haucke, Volker (Author) , Schürmann, Annette (Author) , Birchmeier, Carmen (Author) , Daumke, Oliver (Author)
Format: Article (Journal)
Language:English
Published: March 31, 2020
In: Proceedings of the National Academy of Sciences of the United States of America
Year: 2020, Volume: 117, Issue: 13, Pages: 7471-7481
ISSN:1091-6490
DOI:10.1073/pnas.1918415117
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1073/pnas.1918415117
Verlag, lizenzpflichtig, Volltext: https://www.pnas.org/content/117/13/7471
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Author Notes:Claudia Matthaeus, Ines Lahmann, Séverine Kunz, Wenke Jonas, Arthur Alves Melo, Martin Lehmann, Elin Larsson, Richard Lundmark, Matthias Kern, Matthias Blüher, Hannah Olschowski, Julian Kompa, Britta Brügger, Dominik N. Müller, Volker Haucke, Annette Schürmann, Carmen Birchmeier, and Oliver Daumke
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Summary:Eps15-homology domain containing protein 2 (EHD2) is a dynamin-related ATPase located at the neck of caveolae, but its physiological function has remained unclear. Here, we found that global genetic ablation of EHD2 in mice leads to increased lipid droplet size in fat tissue. This organismic phenotype was paralleled at the cellular level by increased fatty acid uptake via a caveolae- and CD36-dependent pathway that also involves dynamin. Concomitantly, elevated numbers of detached caveolae were found in brown and white adipose tissue lacking EHD2, and increased caveolar mobility in mouse embryonic fibroblasts. EHD2 expression itself was down-regulated in the visceral fat of two obese mouse models and obese patients. Our data suggest that EHD2 controls a cell-autonomous, caveolae-dependent fatty acid uptake pathway and imply that low EHD2 expression levels are linked to obesity.
Item Description:Gesehen am 21.04.2020
Physical Description:Online Resource
ISSN:1091-6490
DOI:10.1073/pnas.1918415117

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