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

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.