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N-terminal processing and modifications of caveolin-1 in caveolae from human adipocytes
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Medicinska fakulteten.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Medicinska fakulteten.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Medicinska fakulteten.
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2004 (Engelska)Ingår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 320, nr 2, s. 480-486Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Caveolin, the principal structural protein of caveolae membrane domains, has a cytosol-exposed N-terminal part that was cleaved off by trypsin treatment of caveolae vesicles isolated from primary human adipocytes. Sequencing of the released tryptic peptides by nanospray quadrupole time-of-flight mass spectrometry revealed that both caveolin-1alpha and caveolin-1beta were processed by excision of the starting methionines. The N-terminus of the mature caveolin-1alpha was acetylated, while caveolin-1beta was found in acetylated as well as in non-acetylated forms. Fractional phosphorylation of serine-36 in the mature caveolin-1alpha and of the homologous serine-5 in caveolin-1beta was identified. This is the first experimental evidence for in vivo phosphorylation of caveolin-1 at the consensus site for phosphorylation by protein kinase C. The phosphorylation was found in both the acetylated and non-acetylated variants of caveolin-1beta. This variability in modifications is consistent with critical involvement of the N-terminal domain of caveolin in the regulation of caveolae.

Ort, förlag, år, upplaga, sidor
2004. Vol. 320, nr 2, s. 480-486
Nyckelord [en]
Human adipocyte, Caveolin-1; Caveolae, Protein phosphorylation, N-terminal acetylation, Mass spectrometry
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:liu:diva-19146DOI: 10.1016/j.bbrc.2004.05.196PubMedID: 15219854OAI: oai:DiVA.org:liu-19146DiVA, id: diva2:223380
Tillgänglig från: 2009-06-12 Skapad: 2009-06-12 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
Ingår i avhandling
1. Expanding role of caveolae in control of adipocyte metabolism: proteomics of caveolae
Öppna denna publikation i ny flik eller fönster >>Expanding role of caveolae in control of adipocyte metabolism: proteomics of caveolae
2006 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Linköping: Linköping University Electronic Press, 2006. s. 54
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 968
Nyckelord
Diabetes, Insulin signalling, Fatty acid metabolism, Proteomics, Mass spectrometry
Nationell ämneskategori
Odontologi
Identifikatorer
urn:nbn:se:liu:diva-8239 (URN)91-85643-58-0 (ISBN)
Disputation
2006-12-01, Berzeliussalen, Campus US, Linköpings Universitet, Linköping, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2007-02-06 Skapad: 2007-02-06 Senast uppdaterad: 2009-06-12Bibliografiskt granskad

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Vainonen, Julia PAboulaich, NabilaTurkina, Maria VStrålfors, PeterVener, Alexander V

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