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Association and insulin regulated translocation of hormone-sensitive lipase with PTRF
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
2006 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, Vol. 350, no 3, 657-661 p.Article in journal (Refereed) Published
Abstract [en]

Polymerase I and transcript release factor (PTRF) is in human adipocytes mainly localized at the plasma membrane. This localization was under control of insulin, which translocated PTRF to the cytosol and nucleus, indicating a novel role for PTRF in insulin transcriptional control. In the plasma membrane PTRF was specifically bound to a triacylglycerol-metabolizing subclass of caveolae containing hormone-sensitive lipase (HSL). In response to insulin PTRF was translocated to the cytosol in parallel with HSL. PTRF and HSL were quantitatively immunoprecipitated from the cytosol by antibodies against either PTRF or HSL. The findings indicate also a novel extranuclear function for PTRF in the control of lipolysis.

Place, publisher, year, edition, pages
2006. Vol. 350, no 3, 657-661 p.
Keyword [en]
Hormone-sensitive lipase, Polymerase I and transcript release factor, Adipocyte, Human, Insulin, Translocation, Protein complex, Caveolae, Lipid metabolism, Transcriptional control
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-19148DOI: 10.1016/j.bbrc.2006.09.094PubMedID: 17026959OAI: oai:DiVA.org:liu-19148DiVA: diva2:223387
Available from: 2009-06-12 Created: 2009-06-12 Last updated: 2009-07-06Bibliographically approved
In thesis
1. Expanding role of caveolae in control of adipocyte metabolism: proteomics of caveolae
Open this publication in new window or tab >>Expanding role of caveolae in control of adipocyte metabolism: proteomics of caveolae
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The primary function of adipose tissue is to store energy in the form of triacylglycerol, which is hydrolyzed to fatty acids to supply other tissues with energy. While insulin promotes the storage of triacylglycerol, catecholamines stimulate its hydrolysis. The development of type II diabetes is strongly associated with obesity, indicating a role of triacylglycerol metabolism in the pathogenesis of diabetes. Caveolae are plasma membrane invaginations found in most cells but are highly abundant in adipocytes. Insulin receptors are localized in caveolae and their function depends on intact caveolae structures. In the present thesis work, mass spectrometry-based methodology allowed identification of a number of new proteins and their posttranslational modifications in caveolae of human adipocytes. Variable N-terminal acetylation and phosphorylation of caveolin-1α and caveolin-1β were identified, which might regulate the function of caveolae. The transcription regulator protein PTRF was identified as the major caveolae associated protein. Specific proteolytic modifications of PTRF at the cytosolic surface of caveolae and phosphorylation on nine serine and one threonine residues were identified. Moreover, insulin induced translocation of PTRF from the plasma membrane to the nucleus. PTRF was previously shown to regulate the activity of both RNA polymerase I and polymerase II, thus a role of PTRF in mediating the anabolic action of insulin on protein synthesis and gene transcription is proposed.

PTRF was also involved in an extranuclear function in the hormonal regulation of triacylglycerol metabolism in caveolae. PTRF was colocalized with the triacylglycerol regulator proteins perilipin and hormone-sensitive lipase (HSL) in the triacylglycerol-synthesizing caveolae subclass. We showed that, while perilipin was translocated to the plasma membrane, both PTRF and HSL were translocated from the plasma membrane to the cytosol as a complex in response to insulin. The perilipin recruited to the plasma membrane was highly threonine phosphorylated. By mass spectrometry, three phosphorylated threonine residues were identified and were located in an acidic domain in the lipid droplet targeting domain of perilipin. The insulin-induced recruitment of perilipin to the plasma membrane might, therefore be phosphorylation-dependent. Isoproterenol, which stimulates hydrolysis of triacylglycerol, induced a complete depletion of perilipin B from the plasma membrane, suggesting a function of perilipin B to protect newly synthesized triacylglycerol in caveolae from being hydrolyzed by HSL. The location of PTRF and HSL was not affected by isoproterenol, indicating that insulin is acting against a default presence of PTRF and HSL in caveolae.

Taken together, this thesis expands our knowledge about caveolae and provided valuable information about their involvement in novel roles, particularly in the hormonal regulation of triacylglycerol metabolism.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2006. 54 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 968
Keyword
Diabetes, Insulin signalling, Fatty acid metabolism, Proteomics, Mass spectrometry
National Category
Dentistry
Identifiers
urn:nbn:se:liu:diva-8239 (URN)91-85643-58-0 (ISBN)
Public defence
2006-12-01, Berzeliussalen, Campus US, Linköpings Universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2007-02-06 Created: 2007-02-06 Last updated: 2009-06-12Bibliographically approved

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