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 journalArticle

6 Citations (Scopus)

Abstract

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
Volume27
Issue number3
DOIs
Publication statusPublished - Apr 2008

Fingerprint

Procollagen
Amyloid
Connective Tissue
Bone Morphogenetic Protein 1
Amyloidosis
Dialysis
Synovial Membrane
Renal Dialysis
proteinase C
Fluorescence Spectrometry
Collagen Type I
Gene Library
Fluorescence Microscopy
Immunoprecipitation
Tendons
Electron Microscopy
Joints
Yeasts

Keywords

  • β2-m amyloid
  • 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

ASJC Scopus subject areas

  • Molecular Biology

Cite this

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

In: Matrix Biology, Vol. 27, No. 3, 04.2008, p. 211-219.

Research output: Contribution to journalArticle

Morimoto, H, Wada, J, Font, B, Mott, JD, Hulmes, DJS, Ookoshi, T, Naiki, H, Yasuhara, A, Nakatsuka, A, Fukuoka, K, Takatori, Y, Ichikawa, H, Akagi, S, Nakao, K & Makino, H 2008, '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', Matrix Biology, vol. 27, no. 3, pp. 211-219. https://doi.org/10.1016/j.matbio.2007.11.005
Morimoto, Hisanori ; Wada, Jun ; Font, Bernard ; Mott, Joni D. ; Hulmes, David J S ; Ookoshi, Tadakazu ; Naiki, Hironobu ; Yasuhara, Akihiro ; Nakatsuka, Atsuko ; Fukuoka, Kousuke ; Takatori, Yuji ; Ichikawa, Haruo ; Akagi, Shigeru ; Nakao, Kazushi ; Makino, Hirofumi. / 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. In: Matrix Biology. 2008 ; Vol. 27, No. 3. pp. 211-219.
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AU - Font, Bernard

AU - Mott, Joni D.

AU - Hulmes, David J S

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AU - Naiki, Hironobu

AU - Yasuhara, Akihiro

AU - Nakatsuka, Atsuko

AU - Fukuoka, Kousuke

AU - Takatori, Yuji

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