Secreted progranulin is a homodimer and is not a component of high density lipoproteins (HDL)

Andrew D. Nguyen, Thi A. Nguyen, Basar Cenik, Gang Yu, Joachim Herz, Tobias C. Walther, W. Sean Davidson, Robert V. Farese

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Progranulin is a secreted glycoprotein, and the GRN gene is mutated in some cases of frontotemporal dementia. Progranulin has also been implicated in cell growth, wound healing, inflammation, and cancer. We investigated the molecular nature of secreted progranulin and provide evidence that progranulin exists as a homodimer. Although recombinant progranulin has a molecular mass of ~85 kDa by SDS-PAGE, it elutes in fractions corresponding to ~170-180 kDa by gel-filtration chromatography. Additionally, recombinant progranulin can be intermolecularly cross-linked, yielding a complex corresponding to a dimer (~180 kDa), and progranulins containing different epitope tags physically interact. In plasma, progranulin similarly forms complexes of ~180-190 kDa. Although progranulin partially co-fractionated with high density lipoproteins (HDL) by gel-filtration chromatography, we found no evidence that progranulin in mouse or human plasma is a component of HDLeither by ultracentrifugation or by lipid binding assays.We conclude that circulating progranulin exists as a dimer and is not likely a component of HDL.

Original languageEnglish (US)
Pages (from-to)8627-8635
Number of pages9
JournalJournal of Biological Chemistry
Volume288
Issue number12
DOIs
StatePublished - Mar 22 2013

Fingerprint

HDL Lipoproteins
Chromatography
Dimers
Gel Chromatography
Gels
Plasma (human)
Frontotemporal Dementia
Ultracentrifugation
Cell growth
Molecular mass
Wound Healing
Epitopes
Polyacrylamide Gel Electrophoresis
Assays
Glycoproteins
Genes
Inflammation
Lipids
Plasmas
Growth

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Secreted progranulin is a homodimer and is not a component of high density lipoproteins (HDL). / Nguyen, Andrew D.; Nguyen, Thi A.; Cenik, Basar; Yu, Gang; Herz, Joachim; Walther, Tobias C.; Davidson, W. Sean; Farese, Robert V.

In: Journal of Biological Chemistry, Vol. 288, No. 12, 22.03.2013, p. 8627-8635.

Research output: Contribution to journalArticle

Nguyen, Andrew D. ; Nguyen, Thi A. ; Cenik, Basar ; Yu, Gang ; Herz, Joachim ; Walther, Tobias C. ; Davidson, W. Sean ; Farese, Robert V. / Secreted progranulin is a homodimer and is not a component of high density lipoproteins (HDL). In: Journal of Biological Chemistry. 2013 ; Vol. 288, No. 12. pp. 8627-8635.
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