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CLAC: a novel Alzheimer amyloid plaque component derived from a transmembrane precursor, CLAC-P/collagen type XXV.

Abstract
We raised monoclonal antibodies against senile plaque (SP) amyloid and obtained a clone 9D2, which labeled amyloid fibrils in SPs and reacted with approximately 50/100 kDa polypeptides in Alzheimer's disease (AD) brains. We purified the 9D2 antigens and cloned a cDNA encoding its precursor, which was a novel type II transmembrane protein specifically expressed in neurons. This precursor harbored three collagen-like Gly-X-Y repeat motifs and was partially homologous to collagen type XIII. Thus, we named the 9D2 antigen as CLAC (collagen-like Alzheimer amyloid plaque component), and its precursor as CLAC-P/collagen type XXV. The extracellular domain of CLAC-P/collagen type XXV was secreted by furin convertase, and the N-terminus of CLAC deposited in AD brains was pyroglutamate modified. Both secreted and membrane-tethered forms of CLAC-P/collagen type XXV specifically bound to fibrillized Abeta, implicating these proteins in beta-amyloidogenesis and neuronal degeneration in AD.
AuthorsTadafumi Hashimoto, Tomoko Wakabayashi, Atsushi Watanabe, Hisatomo Kowa, Ritsuko Hosoda, Atsushi Nakamura, Ichiro Kanazawa, Takao Arai, Koji Takio, David M A Mann, Takeshi Iwatsubo
JournalThe EMBO journal (EMBO J) Vol. 21 Issue 7 Pg. 1524-34 (Apr 02 2002) ISSN: 0261-4189 [Print] England
PMID11927537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Amyloid beta-Peptides
  • Antigens
  • COL25A1 protein, human
  • DNA, Complementary
  • Membrane Proteins
  • Non-Fibrillar Collagens
  • Protein Precursors
  • Collagen
  • Subtilisins
  • Furin
Topics
  • Alzheimer Disease (metabolism, pathology)
  • Amino Acid Sequence
  • Amyloid beta-Peptides (metabolism)
  • Animals
  • Antigens (genetics, isolation & purification, metabolism)
  • Base Sequence
  • Binding Sites
  • Brain (metabolism, pathology, ultrastructure)
  • Collagen (genetics, isolation & purification, metabolism)
  • DNA, Complementary
  • Extracellular Space (metabolism)
  • Furin
  • Gene Expression
  • Humans
  • Membrane Proteins (genetics, isolation & purification, metabolism)
  • Mice
  • Molecular Sequence Data
  • Neurons (metabolism)
  • Non-Fibrillar Collagens
  • Plaque, Amyloid (metabolism)
  • Protein Precursors (genetics, isolation & purification, metabolism)
  • Sequence Homology, Amino Acid
  • Subtilisins (metabolism)

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