Constitutive α-secretase cleavage of the β-amyloid precursor protein in the furin-deficient LoVo cell line: Involvement of the pro-hormone convertase 7 and the disintegrin metalloprotease ADAM10

Academic Article

Abstract

  • The β-amyloid precursor protein (βAPP) undergoes a physiological cleavage triggered by one or several proteolytic activities referred to as α-secretases, leading to the secretion of sAPPα. Several lines of evidence indicate that the α-secretase cleavage is a highly regulated process. Thus, besides constitutive production of sAPPα, several studies have reported on protein kinase C-regulated sAPPα secretion. Studies aimed at identifying α-secretase(s) candidates suggest the involvement of enzymes belonging to the prohormone convertases and disintegrin families. The delineation of respective contributions of proteolytic activities in constitutive and regulated sAPPα secretion is rendered difficult by the fact that the overall regulated response always includes the basal constitutive counterpart that cannot be selectively abolished. Here we report on the fact that the furin-deficient LoVo cells are devoid of regulated PKC-dependent sAPPα secretion and therefore represent an interesting model to study exclusively the constitutive sAPPα secretion. We show here, by a pharmacological approach using selective inhibitors, that pro-hormone convertases and proteases of the ADAM (disintegrin metalloproteases) family participate in the production/secretion of sAPPαs in LoVo cells. Transfection analysis allowed us to further establish that the pro-hormone convertase 7 and ADAM10 but not ADAM17 (TACE, tumour necrosis factor α-converting enzyme) likely contribute to constitutive sAPPα secretion by LoVo cells.
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    Digital Object Identifier (doi)

    Author List

  • Lopez-Perez E; Zhang Y; Frank SJ; Creemers J; Seidah N; Checler F
  • Start Page

  • 1532
  • End Page

  • 1539
  • Volume

  • 76
  • Issue

  • 5