Fibulin‐1 binds the amino‐terminal head of β‐amyloid precursor protein and modulates its physiological function

  title={Fibulin‐1 binds the amino‐terminal head of $\beta$‐amyloid precursor protein and modulates its physiological function},
  author={Ikuroh Ohsawa and Chizuko Takamura and Shinichi Kohsaka},
  journal={Journal of Neurochemistry},
Genetic studies have implicated amyloid precursor protein (APP) in the pathogenesis of Alzheimer's disease. While accumulating lines of evidence indicate that APP has various functions in cells, little is known about the proteins that modulate its biological activity. Toward this end, we employed a two‐hybrid system to identify potential interacting factors. We now report that fibulin‐1, which contains repetitive Ca2+‐binding EGF‐like elements, binds to APP at its amino‐terminal growth factor… 
Identification of a novel amyloid precursor protein processing pathway that generates secreted N‐terminal fragments
  • L. VellaR. Cappai
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2012
SH‐SY5Y studies indicate the generation of APP NTFs involves a novel APP processing pathway, regulated by protein kinase C, but independent of α‐ secretase or β‐secretase 1 (BACE) activity.
The Amyloid Precursor Protein Represses Expression of Acetylcholinesterase in Neuronal Cell Lines*
Whether APP is involved in the regulation of acetylcholinesterase (AChE), which is a key protein of the cholinergic system and has been shown to accelerate amyloid fibril formation and increase their toxicity, is examined and regulated in two neuronal cell lines by APP in a manner independent of the generation of sAPPα, sAPPβ, and AICD.
Metalloprotease Meprin β Generates Nontoxic N-terminal Amyloid Precursor Protein Fragments in Vivo*
It is demonstrated that meprin β is a physiologically relevant enzyme in APP processing, and n-terminal APP fragments were in the range of those responsible for caspase-induced neurodegeneration, and cytotoxicity to primary neurons treated by these fragments was not detected.
The Collagen Chaperone HSP47 Is a New Interactor of APP that Affects the Levels of Extracellular Beta-Amyloid Peptides
HSP47 is unveiled as a new functional interactor of APP and imply it as a potential target for preventing the formation and/or growth amyloid plaques.
Identification of a Region of β-Amyloid Precursor Protein Essential for Its Gelatinase A Inhibitory Activity*
The decapeptide region of APP is likely an active site-directed inhibitor that has high selectivity toward gelatinase A and the complex formation was prevented completely by a hydroxamate-based synthetic inhibitor.
The biological role of the Alzheimer amyloid precursor protein in epithelial cells
An overview on the functions of sAPP as an epithelial growth factor is presented and it is suggested that Proliferation and migration are known to be part of complex processes such as wound healing which, therefore, might be facilitated by the growth factor function of s APP.
The amyloid precursor protein and postnatal neurogenesis/neuroregeneration.
Identification of Amino Acid Residues of the Matrix Metalloproteinase-2 Essential for Its Selective Inhibition by β-Amyloid Precursor Protein-derived Inhibitor*
It is speculated that the direction of interaction makes the active site-bound APP-IP resistant to cleavage, thereby supporting the inhibitory action of the peptide inhibitor.


Crystal structure of the N-terminal, growth factor-like domain of Alzheimer amyloid precursor protein
Structural similarities with cysteine-rich growth factors, taken together with its known growth-promoting properties, suggests the APP N-terminal domain could function as a growth factor in vivo.
Isoform‐Specific Modulation by Apolipoprotein E of the Activities of Secreted β‐Amyloid Precursor Protein
Kinetic analyses and coimmunoprecipitation experiments indicated that sAPP‐dependent neuroprotective mechanisms would be compromised in individuals expressing ApoE4, a scenario that may contribute to the development of Alzheimer's disease.
Plasminogen Binds Specifically to α‐Enolase on Rat Neuronal Plasma Membrane
Results suggest that α‐enolase may function as a PGn‐binding molecule on the neuronal cell surface, as well as showing that PGn binds specifically to a protein with a molecular mass of 45 kDa in the neuronal plasma membrane.
Ligand-dependent G Protein Coupling Function of Amyloid Transmembrane Precursor (*)
In phospholipid vesicles consisting of baculovirally made APP695 and brain trimeric Go, 22C11, a monoclonal antibody against the extracellular domain of APP, increased GTPγS binding and the turnover number of GTPase of Go without affecting its intrinsic GTP enzyme activity.
Amino acid sequence RERMS represents the active domain of amyloid beta/A4 protein precursor that promotes fibroblast growth
A battery of synthetic peptides was applied on this bioassay and found that the sequence of five amino acids, RERMS, was uniquely required for the growth-promoting activity of sAPP-695, and the activity was sequence- specific because the reverse-sequence peptide of the active domain had no activity.
The Amyloid Precursor Protein Interacts with Go Heterotrimeric Protein within a Cell Compartment Specialized in Signal Transduction
In strong contrast with results obtained with reconstituted phospholipid vesicles, it is found that incubating total neuronal membranes with 22C11, an antibody that recognizes an N-terminal βAPP epitope, reduces high-affinity Go GTPase activity.
Increased Activity‐Regulating and Neuroprotective Efficacy of α‐Secretase‐Derived Secreted Amyloid Precursor Protein Conferred by a C‐Terminal Heparin‐Binding Domain
Findings indicate that alternative processing of βAPP has profound effects on the bioactivity of the resultant sAPP products and suggest that reduced levels of sAPPα could contribute to neuronal degeneration in Alzhiemer's disease.
Secreted Forms of β‐Amyloid Precursor Protein Protect Against Ischemic Brain Injury
It is reported that postischemic administration of these APPSs intracerebroventricularly protects neurons in the CA1 region of rat hippocampus against ischemic injury, and this data provide direct evidence for a neuroprotective action ofAPPSs in vivo.
Amino‐terminal region of secreted form of amyloid precursor protein stimulates proliferation of neural stem cells
It is found that the secreted form of APP (sAPP) significantly enhanced proliferation of neural stem cells in vivo and plays an important role during the early CNS development.
Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E
It is found that treatment with sAPP-α increased markers of activation in microglia and enhanced their production of neurotoxins, indicating that increased amyloidogenic processing could adversely affect the balance of sAPP activities that determine neuronal viability.