Perilipin 1 binds to aquaporin 7 in human adipocytes and controls its mobility via protein kinase A mediated phosphorylation
(2016) In Metabolism, Clinical and Experimental 65(12). p.1731-1742- Abstract
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... (More)
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.
(Less)
- author
- organization
-
- EXODIAB: Excellence of Diabetes Research in Sweden
- Medical Structural Biology (research group)
- Medical Protein Science (research group)
- Glucose Transport and Protein Trafficking (research group)
- Molecular Endocrinology (research group)
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- publishing date
- 2016-12-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adipocyte, Aquaporin 7, Glycerol, Perilipin 1, PKA
- in
- Metabolism, Clinical and Experimental
- volume
- 65
- issue
- 12
- pages
- 12 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:27832861
- wos:000388158700004
- scopus:85007566049
- ISSN
- 0026-0495
- DOI
- 10.1016/j.metabol.2016.09.004
- language
- English
- LU publication?
- yes
- id
- dffff6bf-ec34-493e-9c3a-b99ebe2aa117
- date added to LUP
- 2017-01-13 09:43:23
- date last changed
- 2024-09-08 05:15:09
@article{dffff6bf-ec34-493e-9c3a-b99ebe2aa117, abstract = {{<p>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.</p>}}, author = {{Söndergaard Hansen, Jesper and Krintel, Christian and Hernebring, Malin and Haataja, Tatu J K and de Marè, Sofia and Wasserstrom, Sebastian and Kosinska-Eriksson, Urszula and Palmgren, Madelene and Holm, Cecilia and Stenkula, Karin G. and Jones, Helena A. and Lindkvist-Petersson, Karin}}, issn = {{0026-0495}}, keywords = {{Adipocyte; Aquaporin 7; Glycerol; Perilipin 1; PKA}}, language = {{eng}}, month = {{12}}, number = {{12}}, pages = {{1731--1742}}, publisher = {{Elsevier}}, series = {{Metabolism, Clinical and Experimental}}, title = {{Perilipin 1 binds to aquaporin 7 in human adipocytes and controls its mobility via protein kinase A mediated phosphorylation}}, url = {{http://dx.doi.org/10.1016/j.metabol.2016.09.004}}, doi = {{10.1016/j.metabol.2016.09.004}}, volume = {{65}}, year = {{2016}}, }