APP family member dimeric complexes are formed predominantly in synaptic compartments

Cell & Bioscience

Research

Sandra Teigler¹  Virginie Adam¹  Stefan Kins¹  Mathieu Meleux¹  Alexander August¹  Sandra Schilling¹  Carolin Conradt¹  Simone Eggert²  Luisa M. Tremmel³  Edward H. Koo⁴  Ulrike C. Müller⁵ 

[1] Department of Human Biology and Human Genetics, University of Kaiserslautern, 67663, Kaiserslautern, Germany;Department of Human Biology and Human Genetics, University of Kaiserslautern, 67663, Kaiserslautern, Germany;Department of Neurogenetics, Max-Planck-Institute for Multidisciplinary Sciences, City-Campus, Hermann-Rein-Str. 3, 37075, Göttingen, Germany;Department of Human Biology and Human Genetics, University of Kaiserslautern, 67663, Kaiserslautern, Germany;Medical, Biochemistry & Molecular Biology, Center for Molecular Signaling (PZMS), Saarland University, 66421, Homburg, Germany;Department of Neuroscience, University of California, San Diego (UCSD), 92093-0662, La Jolla, CA, USA;Institute for Pharmacy and Molecular Biotechnology, University of Heidelberg, 69120, Heidelberg, Germany;

关键词: Alzheimer’s disease;    Amyloid precursor protein;    APLP1;    APLP2;    Dimerization;    Synaptosomes;    Blue Native gels;   

DOI  :  10.1186/s13578-023-01092-6

 received in 2023-03-03, accepted in 2023-07-21,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe amyloid precursor protein (APP), a key player in Alzheimer’s disease (AD), is part of a larger gene family, including the APP like proteins APLP1 and APLP2. They share similar structures, form homo- and heterotypic dimers and exhibit overlapping functions.ResultsWe investigated complex formation of the APP family members via two inducible dimerization systems, the FKBP-rapamycin based dimerization as well as cysteine induced dimerization, combined with co-immunoprecipitations and Blue Native (BN) gel analyses. Within the APP family, APLP1 shows the highest degree of dimerization and high molecular weight (HMW) complex formation. Interestingly, only about 20% of APP is dimerized in cultured cells whereas up to 50% of APP is dimerized in mouse brains, independent of age and splice forms. Furthermore, we could show that dimerized APP originates mostly from neurons and is enriched in synaptosomes. Finally, BN gel analysis of human cortex samples shows a significant decrease of APP dimers in AD patients compared to controls.ConclusionsTogether, we suggest that loss of full-length APP dimers might correlate with loss of synapses in the process of AD.

【 授权许可】

CC BY   
© The Author(s) 2023

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