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Hashimoto, T, Wakabayashi, T, Watanabe, A, Kowa, H, Hosoda, R, Nakamura, A, Kanazawa, I, Arai, T, Takio, K, Mann, DM and Iwatsubo, T (2002) CLAC: a novel Alzheimer amyloid plaque component derived from a transmembrane precursor, CLAC-P/collagen type XXV. EMBO J. 21:1524-34
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.
Alzheimer Disease/metabolism; Alzheimer Disease/pathology; Amino Acid Sequence; Amyloid beta-Peptides/metabolism; Animals; Antigens/genetics; Antigens/isolation & purification; Antigens/metabolism; Base Sequence; Binding Sites; Brain/metabolism; Brain/pathology; Brain/ultrastructure; Collagen/genetics; Collagen/isolation & purification; Collagen/metabolism; DNA, Complementary; Extracellular Space/metabolism; Furin; Gene Expression; Humans; Membrane Proteins/genetics; Membrane Proteins/isolation & purification; Membrane Proteins/metabolism; Mice; Molecular Sequence Data; Neurons/metabolism; Non-Fibrillar Collagens; Plaque, Amyloid/metabolism; Protein Precursors/genetics; Protein Precursors/isolation & purification; Protein Precursors/metabolism; Sequence Homology, Amino Acid; Subtilisins/metabolism
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