Perilipin 1 binds to aquaporin 7 in human adipocytes and controls its mobility via protein kinase A mediated phosphorylation.
Accumulating evidence suggests that dysregulated glycerol metabolism contributes to the pathophysiology of obesity and type 2 diabetes. Glycerol efflux from adipocytes is regulated by the aquaglyceroporin AQP7, which is translocated upon hormone stimulation. Here, we propose a molecular mechanism where the AQP7 mobility in adipocytes is dependent on perilipin 1 and protein kinase A. Biochemical analyses combined with ex vivo studies in human primary adipocytes, demonstrate that perilipin 1 binds to AQP7, and that catecholamine activated protein kinase A phosphorylates the N-terminus of AQP7, thereby reducing complex formation. Together, these findings are indicative of how glycerol release is controlled in adipocytes, and may pave the way for the future design of drugs against human metabolic pathologies.
Department of Experimental Medical Science, Lund University, BMC, 221 84, Lund, Sweden.
Jesper S
JS
Hansen
Department of Experimental Medical Science, Lund University, BMC, 221 84, Lund, Sweden.
Christian
C
Krintel
Department of Experimental Medical Science, Lund University, BMC, 221 84, Lund, Sweden.
Malin
M
Hernebring
Department of Experimental Medical Science, Lund University, BMC, 221 84, Lund, Sweden.
Tatu J K
TJ
Haataja
Department of Experimental Medical Science, Lund University, BMC, 221 84, Lund, Sweden.
Sofia
S
de Marè
Department of Experimental Medical Science, Lund University, BMC, 221 84, Lund, Sweden.
Sebastian
S
Wasserstrom
Department of Chemistry and Molecular Biology, University of Gothenburg, 405 30, Gothenburg, Sweden.
Urszula
U
Kosinska-Eriksson
Department of Chemistry and Molecular Biology, University of Gothenburg, 405 30, Gothenburg, Sweden.
Madelene
M
Palmgren
Department of Experimental Medical Science, Lund University, BMC, 221 84, Lund, Sweden.
Cecilia
C
Holm
Department of Experimental Medical Science, Lund University, BMC, 221 84, Lund, Sweden.
Karin G
KG
Stenkula
Department of Experimental Medical Science, Lund University, BMC, 221 84, Lund, Sweden.
Helena A
HA
Jones
Department of Experimental Medical Science, Lund University, BMC, 221 84, Lund, Sweden. Electronic address: karin.lindkvist@med.lu.se.
Karin
K
Lindkvist-Petersson
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D020346:Aquaporins / Q000378:metabolism*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D000070778:Perilipin-1 / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding
C114141:AQP7 protein, human; D020346:Aquaporins; D000070778:Perilipin-1; D017868:Cyclic AMP-Dependent Protein Kinases; D005990:Glycerol
Adipocyte; Aquaporin 7; Glycerol; PKA; Perilipin 1