PAT1a Modulates Intracellular Transport and Processing of Amyloid Precursor 
Protein (APP), APLP1, and APLP2

Kuan, Yung-Hui; Gruebl, Tomas; Soba, Peter; Eggert, Simone; Nesic, Iva; Back, Simone; Kirsch, Joachim; Beyreuther, Konrad; Kins, Stefan

doi:10.1074/jbc.M605407200

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PAT1a Modulates Intracellular Transport and Processing of Amyloid Precursor Protein (APP), APLP1, and APLP2

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Citation

Kuan, Y.-H., Gruebl, T., Soba, P., Eggert, S., Nesic, I., Back, S., et al. (2006). PAT1a Modulates Intracellular Transport and Processing of Amyloid Precursor Protein (APP), APLP1, and APLP2. Journal of Biological Chemistry, 281(52), 40114-40123. doi:10.1074/jbc.M605407200.

Cite as: https://hdl.handle.net/21.11116/0000-000E-3E1C-F

Abstract

Understanding the intracellular transport of the β-amyloid precursor protein (APP) is a major key to elucidate the regulation of APP processing and thus β-amyloid peptide generation in Alzheimer disease pathogenesis. APP and its two paralogues, APLP1 and APLP2 (APLPs), are processed in a very similar manner by the same protease activities. A putative candidate involved in APP transport is protein interacting with APP tail 1 (PAT1), which was reported to interact with the APP intracellular domain. We show that PAT1a, which is 99.0% identical to PAT1, binds to APP, APLP1, and APLP2 in vivo and describe their co-localization in trans-Golgi network vesicles or endosomes in primary neurons. We further demonstrate a direct interaction of PAT1a with the basolateral sorting signal of APP/APLPs. Moreover, we provide evidence for a direct role of PAT1a in APP/APLP transport as overexpression or RNA interference-mediated knockdown of PAT1a modulates APP/APLPs levels at the cell surface. Finally, we show that PAT1a promotes APP/APLPs processing, resulting in increased secretion ofβ-amyloid peptide. Taken together, our data establish PAT1a as a functional link between APP/APLPs transport and their processing.