title: Prohibitin/annexin 2 interaction regulates fatty acid transport in adipose tissue.
abstract: We have previously identified prohibitin (PHB) and annexin A2 (ANX2) as proteins interacting on the surface of vascular endothelial cells in white adipose tissue (WAT) of humans and mice. Here, we demonstrate that ANX2 and PHB also interact in adipocytes. Mice lacking ANX2 have normal WAT vascularization, adipogenesis, and glucose metabolism but display WAT hypotrophy due to reduced fatty acid uptake by WAT endothelium and adipocytes. By using cell culture systems in which ANX2/PHB binding is disrupted either genetically or through treatment with a blocking peptide, we show that fatty acid transport efficiency relies on this protein complex. We also provide evidence that the interaction between ANX2 and PHB mediates fatty acid transport from the endothelium into adipocytes. Moreover, we demonstrate that ANX2 and PHB form a complex with the fatty acid transporter CD36. Finally, we show that the colocalization of PHB and CD36 on adipocyte surface is induced by extracellular fatty acids. Together, our results suggest that an unrecognized biochemical interaction between ANX2 and PHB regulates CD36-mediated fatty acid transport in WAT, thus revealing a new potential pathway for intervention in metabolic diseases.
authors.affiliation: Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Salameh
authors.affiliation: Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Alexes C
authors.initials: AC
authors.lastname: Daquinag
authors.affiliation: University of New Mexico Comprehensive Cancer Center and Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
authors.forename: Daniela I
authors.initials: DI
authors.lastname: Staquicini
authors.affiliation: Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: An
authors.affiliation: Departments of Pediatrics, Cell and Developmental Biology, and Medicine, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hajjar
authors.affiliation: University of New Mexico Comprehensive Cancer Center and Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
authors.forename: Renata
authors.initials: R
authors.lastname: Pasqualini
authors.affiliation: University of New Mexico Comprehensive Cancer Center and Division of Hematology/Oncology, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
authors.forename: Wadih
authors.initials: W
authors.lastname: Arap
authors.affiliation: Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Mikhail G
authors.initials: MG
authors.lastname: Kolonin