Procollagen C-proteinase enhancer-1 (PCPE-1) interacts with β2-microglobulin (β2-m) and may help initiate β2-m amyloid fibril formation in connective tissues

Hisanori Morimoto, Jun Wada, Bernard Font, Joni D. Mott, David J.S. Hulmes, Tadakazu Ookoshi, Hironobu Naiki, Akihiro Yasuhara, Atsuko Nakatsuka, Kousuke Fukuoka, Yuji Takatori, Haruo Ichikawa, Shigeru Akagi, Kazushi Nakao, Hirofumi Makino

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Dialysis related amyloidosis (DRA) is a progressive and serious complication in patients under long-term hemodialysis and mainly leads to osteo-articular diseases. Although β2-microglobulin (β2-m) is the major structural component of β2-m amyloid fibrils, the initiation of amyloid formation is not clearly understood. Here, we have identified procollagen C-proteinase enhancer-1 (PCPE-1) as a new interacting protein with β2-m by screening a human synovium cDNA library. The interaction of β2-m with full-length PCPE-1 was confirmed by immunoprecipitation, solid-phase binding and pull-down assays. By yeast two-hybrid analysis and pull-down assay, β2-m appeared to interact with PCPE-1 via the NTR (netrin-like) domain and not via the CUB (C1r/C1s, Uegf and BMP-1) domain region. In synovial tissues derived from hemodialysis patients with DRA, β2-m co-localized and formed a complex with PCPE-1. β2-m did not alter the basal activity of bone morphogenetic protein-1/procollagen C-proteinase (BMP-1/PCP) nor BMP-1/PCP activity enhanced by PCPE-1. PCPE-1 did not stimulate β2-m amyloid fibril formation from monomeric β2-m in vitro under acidic and neutral conditions as revealed by thioflavin T fluorescence spectroscopy and electron microscopy. Since PCPE-1 is abundantly expressed in connective tissues rich in type I collagen, it may be involved in the initial accumulation of β2-m in selected tissues such as tendon, synovium and bone. Furthermore, since such preferential deposition of β2-m may be linked to subsequent β2-m amyloid fibril formation, the disruption of the interaction between β2-m and PCPE-1 may prevent β2-m amyloid fibril formation and therefore PCPE-1 could be a new target for the treatment of DRA.

Original languageEnglish
Pages (from-to)211-219
Number of pages9
JournalMatrix Biology
Issue number3
Publication statusPublished - Apr 2008


  • Bone morphogenetic protein-1 (BMP-1)
  • CUB (C1r/C1s
  • Dialysis related amyloidosis (DRA)
  • NTR (netrin-like) domain
  • Procollagen C-proteinase (PCP)
  • Procollagen C-proteinase enhancer protein-1 (PCPE-1)
  • Uegf and BMP-1) domain
  • β2-m amyloid

ASJC Scopus subject areas

  • Molecular Biology


Dive into the research topics of 'Procollagen C-proteinase enhancer-1 (PCPE-1) interacts with β2-microglobulin (β2-m) and may help initiate β2-m amyloid fibril formation in connective tissues'. Together they form a unique fingerprint.

Cite this