EHD2-mediated restriction of caveolar dynamics regulates cellular lipid uptake
By
Claudia Matthäus,
Ines Lahmann,
Séverine Kunz,
Wenke Jonas,
Arthur Alves Melo,
Martin Lehmann,
Elin Larsson,
Richard Lundmark,
Matthias Kern,
Matthias Blüher,
Dominik N. Müller,
Volker Haucke,
Annette Schürmann,
Carmen Birchmeier,
Oliver Daumke
Posted 04 Jan 2019
bioRxiv DOI: 10.1101/511709
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 led to increased fat accumulation. This organismic phenotype was paralleled at the cellular level by increased lipid uptake via a caveolae-, dynamin- and CD36-dependent pathway, an elevated number of detached caveolae and higher caveolar mobility. Furthermore, 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 lipid uptake pathway and suggest that low EHD2 expression levels are linked to obesity.
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