AP-4 complex subunit mu-1 (AP4M1) can recognise and interact with tyrosine-based (YXXphi) sorting signals found within the cytoplasmic tails of integral membrane proteins such as the amyloid precursor protein (APP), implicated in Alzheimer's disease. Once bound to AP4M1, APP is transported from the trans-Golgi network (TGN) to endosomes, thereby reducing amyloidogenic processing of the protein. Disruption of this interaction decreases localisation of APP to endosomes and enhances gamma-secretase-catalysed cleavage of APP to the pathogenic amyloid-beta peptide (Burgos et al. 2010).
Prabhu, Y, Hurley, JH, Mardones, GA, Burgos, PV, Rojas, AL, Bonifacino, JS, daSilva, LL
protein transmembrane transporter activity of AP4:APP [trans-Golgi network membrane]
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