Implication of the proprotein convertase NARC‐1/PCSK9 in the development of the nervous system

• DOI: 10.1111/j.1471-4159.2006.03928.x
• Publication Date: 2006-06-26T16:14:28Z
• Authors: Steve Poirier; Annik Prat; Edwige Marcinkiewicz; Joanne Paquin; Babykumari P. Chi...; David Baranowski; Benoit Cadieux; Hugh P. J. Bennett; Nabil G. Seidah
• Keywords: PCSK9; Proprotein Convertases; Proprotein Convertases; Kexin

Abstract Neural apoptosis‐regulated convertase‐1/proprotein convertase subtilisin‐kexin like‐9 (NARC‐1/PCSK9) is a proprotein recently described to play major role in cholesterol homeostasis through enhanced degradation of the low‐density lipoprotein receptor (LDLR) and possibly neural development. Herein, we investigated potential involvement this proteinase development CNS using mouse embryonal pluripotent P19 cells zebrafish as models. Time course quantitative RT–PCR analyses were performed following retinoic acid (RA)‐induced neuroectodermal differentiation cells. Accordingly, mRNA levels NARC‐1/PCSK9 peaked at day 2 fell off thereafter. In contrast, expression convertases subtilisin kexin isozyme 1/site 1 protease Furin was unaffected by RA, whereas that PC5/6 PC2 increased within and/or after first 4 days period respectively. This pattern not affected cholesterogenic transcription factor sterol regulatory element‐binding protein‐2, which normally up‐regulates liver. Furthermore, cells, RA treatment did affect protein level endogenous LDLR. agrees with unique rodent CNS, including cerebellum, where LDLR significantly expressed. Whole‐mount situ hybridization revealed similar both periphery. Specific knockdown resulted general disorganization cerebellar neurons loss hindbrain–midbrain boundaries, leading embryonic death ∼ 96 h fertilization. These data support novel for development, distinct from organs such