CLAC: a novel Alzheimer amyloid plaque component derived from a transmembrane precursor, CLAC-P/collagen type XXV.
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.
Hashimoto
Tadafumi
T
Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033.
Wakabayashi
Tomoko
T
Watanabe
Atsushi
A
Kowa
Hisatomo
H
Hosoda
Ritsuko
R
Nakamura
Atsushi
A
Kanazawa
Ichiro
I
Arai
Takao
T
Takio
Koji
K
Mann
David M A
DM
Iwatsubo
Takeshi
T
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D003094:Collagen / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018076:DNA, Complementary; D005110:Extracellular Space / Q000378:metabolism; D045683:Furin; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D024041:Non-Fibrillar Collagens; D058225:Plaque, Amyloid / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013381:Subtilisins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000941:Antigens; C456021:COL25A1 protein, human; D018076:DNA, Complementary; D008565:Membrane Proteins; D024041:Non-Fibrillar Collagens; D011498:Protein Precursors; D003094:Collagen; D013381:Subtilisins; D045683:Furin