title: Is there a link between proprotein convertase PC7 activity and human lipid homeostasis?
abstract: A genome-wide association study suggested that a R504H mutation in the proprotein convertase PC7 is associated with increased circulating levels of HDL and reduced triglycerides in black Africans. Our present results show that PC7 and PC7-R504H exhibit similar processing of transferrin receptor-1, proSortilin, and apolipoprotein-F. Plasma analyses revealed no change in the lipid profiles, insulin or glucose of wild type and PC7 KO mice. Thus, the R504H mutation does not modify the proteolytic activity of PC7. The mechanisms behind the implication of PC7 in the regulation of human HDL, triglycerides and in modifying the levels of atherogenic small dense LDL remain to be elucidated.
authors.affiliation: Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal (IRCM), Affiliated to the University of Montreal, 110 Pine Ave West, Montreal, Quebec H2W 1R7, Canada.
authors.forename: Johann
authors.initials: J
authors.lastname: Guillemot
authors.affiliation: Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal (IRCM), Affiliated to the University of Montreal, 110 Pine Ave West, Montreal, Quebec H2W 1R7, Canada.
authors.forename: Rachid
authors.initials: R
authors.lastname: Essalmani
authors.affiliation: Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal (IRCM), Affiliated to the University of Montreal, 110 Pine Ave West, Montreal, Quebec H2W 1R7, Canada.
authors.forename: Josée
authors.initials: J
authors.lastname: Hamelin
authors.affiliation: Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal (IRCM), Affiliated to the University of Montreal, 110 Pine Ave West, Montreal, Quebec H2W 1R7, Canada.
authors.forename: Nabil G
authors.initials: NG
authors.lastname: Seidah
keywords: ANGPTL3, angiopoietin-like 3; ANGPTL4, angiopoietin-like 4; ApoF, apolipoprotein-F; Apolipoprotein F; GOF, gain of function; GWAS, genome-wide association study; HDL, high-density lipoprotein; HDL/LDL; KO, knockout; LDL, low-density lipoprotein; PCs, proprotein convertases; Proprotein convertase PC7; SNP, single nucleotide polymorphism; Sortilin; TGN, trans Golgi network; TMD, transmembrane domain; Transferrin receptor 1; Triglycerides; VLDL, very low-density lipoprotein; hTfR1, human PC7-substrates: transferrin receptor 1