Premium
Two‐dimensional gel mapping of the processing of the human amyloid precursor protein in rat hippocampal neurons
Author(s) -
Simons Mikael,
Tienari Pentti J.,
Dotti Carlos G.,
Beyreuther Konrad
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00654-r
Subject(s) - amyloid precursor protein , hippocampal formation , secretion , semliki forest virus , glycosylation , mutant , protein precursor , microbiology and biotechnology , cleavage (geology) , amyloid precursor protein secretase , alpha secretase , chemistry , biology , biochemistry , alzheimer's disease , neuroscience , gene , medicine , rna , paleontology , disease , fracture (geology)
The proteolytic fragments derived from the amyloid precursor protein (APP) in primary cultures of rat hippocampal neurons were analyzed by two‐dimensional gel electrophoresis. The Semliki Forest Virus expression vector was used to express human APP695 and a mutant form associated with familial Alzheimer's disease (APP‐FAD670/671). Hippocampal neurons expressing wtAPP695 or APP‐FAD670/671 secrete at least six APP fragments of 100–110 kDa with isoelectric focusing points ranging from 4.5 to 4.0. The heterogeneity of the secreted APP forms is shown to be in part due to differences in glycosylation. In contrast to wtAPP695, neurons producing the APP‐FAD670/ 671 variant did not secrete detectable amounts of secretory APP derived from cleavage within the amyloid βA4 domain. This result suggests that there is little α‐secretase cleavage in neurons expressing the APP‐FAD670/671 mutant.