Engulfment adapter PTB domain containing 1 interacts with and affects processing of the amyloid-beta precursor protein
2010 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 33, no 4, 732-743 p.Article in journal (Refereed) Published
Previous studies identified engulfment adapter phosphotyrosine binding (PTB) domain containing 1 (GULP1) as an NPXY-motif interactor of low-density lipoprotein receptor-related protein 1 (LRP1) and suggested a potential relevance in Alzheimer's disease (AD). Since AD associated proteins amyloid-beta A4 precursor protein (APP) and LRP1 were shown to interact with the PTB domain of Fe65 and several other adapters via their intracellular NPXY-motifs, we examined a possible interaction of GULP1 PTB domain with the YENPTY-motif of APP. Here we demonstrate that GULP1 is present in human hippocampal and neocortical neurons. Confocal live cell imaging revealed that coexpressed and endogenous GULP1 colocalizes with APP in the Golgi and endoplasmic reticulum. Analysis of the interacting domains by co-immunoprecipitation of point and deletion mutants revealed that the interaction depends on the PTB domain of GULP1 and the YENPTY-motif of APP. Coexpression of GULP1 affected APP cell surface localization and suppressed generation of Abeta40/42 and sAPPalpha. Taken together, these data identify GULP1 as a novel neuronal APP interacting protein that alters trafficking and processing of APP.
Place, publisher, year, edition, pages
Elsevier, 2010. Vol. 33, no 4, 732-743 p.
APP processing, GULP1, PTB domain, abeta, sAPP secretion
IdentifiersURN: urn:nbn:se:uu:diva-164937DOI: 10.1016/j.neurobiolaging.2010.06.006PubMedID: 20674096OAI: oai:DiVA.org:uu-164937DiVA: diva2:470948