title: Mint2/X11-like colocalizes with the Alzheimer's disease amyloid precursor protein and is associated with neuritic plaques in Alzheimer's disease.
abstract: Aberrant metabolism of the amyloid precursor protein (APP) is believed to be at least part of the pathogenic process in Alzheimer's disease. The carboxy-terminus of APP has been shown to interact with the Mint/X11 family of phosphotyrosine binding (PTB) domain-bearing proteins. It is via their PTB domains that the Mints/X11s bind to APP. Here we report the cloning of full-length mouse Mint2 and demonstrate that in primary cortical neurons, Mint2 and APP share highly similar distributions. Mint2 also colocalizes with APP in transfected CHO cells. In Mint2/APP-cotransfected cells, Mint2 reorganizes the subcellular distribution of APP and also increases the steady-state levels of APP. Finally, we demonstrate that Mint2 is associated with the neuritic plaques found in Alzheimer's disease but not with neurofibrillary tangles. These results are consistent with a role for Mint2 in APP metabolism and trafficking, and suggest a possible role for the Mints/X11s in the pathogenesis of Alzheimer's disease.
authors.affiliation: Department of Neuroscience, The Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: McLoughlin
authors.forename: N G
authors.initials: NG
authors.lastname: Irving
authors.forename: J
authors.initials: J
authors.lastname: Brownlees
authors.forename: J P
authors.initials: JP
authors.lastname: Brion
authors.forename: K
authors.initials: K
authors.lastname: Leroy
authors.forename: C C
authors.initials: CC
authors.lastname: Miller
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D016466:CHO Cells; D015820:Cadherins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006224:Cricetinae; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D058225:Plaque, Amyloid / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution / Q000502:physiology; D014162:Transfection
chemical_list: C491636:APBA2 protein, human; D016564:Amyloid beta-Protein Precursor; C491635:Apba2 protein, mouse; D015820:Cadherins; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins