title: Cross-linking of beta-amyloid protein precursor catalyzed by tissue transglutaminase.
abstract: Alzheimer's disease is characterized by progressive dementia, cortical atrophy with synaptic loss, and the accumulation of neurofibrillary tangles and senile plaques containing beta-amyloid. The beta-amyloid protein precursor (beta-APP), may normally be involved in cell adhesion related to synaptic maintenance. Loss of synapses correlates with dementia, suggesting that synaptic deficits may underlie the disease. Synapse stability may depend on the action of tissue transglutaminase (tTG), an enzyme capable of crosslinking large, multi-domain extracellular glycoproteins, that is active and present at synapses. We now show that beta-APP is a substrate for tTG in vitro that results in dimers and multimers by silver staining and immunoblotting. This novel post-translational modification suggests further roles for beta-APP in synaptic function as well as in Alzheimer's disease.
authors.affiliation: Neurobiology Research Laboratory (151R), VA Medical Center, Kansas City, MO 64128.
authors.forename: G J
authors.initials: GJ
authors.lastname: Ho
authors.forename: E J
authors.initials: EJ
authors.lastname: Gregory
authors.forename: I V
authors.initials: IV
authors.lastname: Smirnova
authors.forename: M N
authors.initials: MN
authors.lastname: Zoubine
authors.forename: B W
authors.initials: BW
authors.lastname: Festoff
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003432:Cross-Linking Reagents; D006168:Guinea Pigs; D006801:Humans; D008099:Liver / Q000201:enzymology; D011994:Recombinant Proteins / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D003432:Cross-Linking Reagents; D011994:Recombinant Proteins; D011503:Transglutaminases