Cellular processing and proteoglycan nature of amyloid precursor proteins.
Amyloid beta protein (beta/A4 or A beta), the main proteinaceous component of the amyloid depositions of the Alzheimer's brain, derives from the proteolytic processing of the amyloid precursor protein (APP). Cleavage of the amyloid precursor by at least two distinct secretase activities produces soluble secreted APP. The major secretase cleavage (site I) takes place between A beta 16 and 17, while the minor cleavage (site II) takes place after A beta Lys 28 and may produce potentially amyloidogenic secreted APP. Full-length cellular APP is cleaved by secretase intracellularly in the Trans-Golgi Network (TGN) or in post-Golgi vesicles. The resultant soluble APP is transported to the plasma membrane and exocytosed. The biological activity of the APP is still not completely understood, although it seems to act as a cell adhesion molecule. Recent studies have shown that in glioma cells, most of the soluble secreted APP occurs as a chondroitin sulfate proteoglycan (CSPG). In addition, full length APP CSPG has been detected in neuroblastoma and fibroblast cells as well as on the surface of glioma cells, and in human brain. These results suggest that the proteoglycan nature of the APP proteins may be important for their biological function.
Robakis
N K
NK
Department of Psychiatry and Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, New York 10029.
Vassilacopoulou
D
D
Efthimiopoulos
S
S
Sambamurti
K
K
Refolo
L M
LM
Shioi
J
J
D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007668:Kidney; D008247:Lysosomes / Q000378:metabolism; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D011499:Protein Processing, Post-Translational; D011509:Proteoglycans / Q000378:metabolism*; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D011508:Chondroitin Sulfate Proteoglycans; D009414:Nerve Growth Factors; D011509:Proteoglycans; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human