PAT1a modulates intracellular transport and processing of amyloid precursor protein (APP), APLP1, and APLP2.
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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.
in: J BIOL CHEM, Jahrgang 281, Nr. 52, 52, 2006, S. 40114-40123.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - PAT1a modulates intracellular transport and processing of amyloid precursor protein (APP), APLP1, and APLP2.
AU - Kuan, Yung-Hui
AU - Gruebl, Tomas
AU - Soba, Peter
AU - Eggert, Simone
AU - Nesic, Iva
AU - Back, Simone
AU - Kirsch, Joachim
AU - Beyreuther, Konrad
AU - Kins, Stefan
PY - 2006
Y1 - 2006
N2 - Understanding the intracellular transport of the beta-amyloid precursor protein (APP) is a major key to elucidate the regulation of APP processing and thus beta-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 of beta-amyloid peptide. Taken together, our data establish PAT1a as a functional link between APP/APLPs transport and their processing.
AB - Understanding the intracellular transport of the beta-amyloid precursor protein (APP) is a major key to elucidate the regulation of APP processing and thus beta-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 of beta-amyloid peptide. Taken together, our data establish PAT1a as a functional link between APP/APLPs transport and their processing.
KW - Animals
KW - Humans
KW - Mice
KW - COS Cells
KW - Cercopithecus aethiops
KW - Cell Line, Tumor
KW - Hydrolysis
KW - Adaptor Proteins, Signal Transducing/genetics
KW - Nerve Tissue Proteins/metabolism
KW - Alzheimer Disease/enzymology/metabolism
KW - Amino Acid Transport Systems/genetics/physiology
KW - Amyloid Precursor Protein Secretases/metabolism
KW - Amyloid beta-Protein Precursor/biosynthesis/metabolism
KW - Protein Binding/genetics
KW - Protein Processing, Post-Translational/genetics
KW - Protein Transport/genetics
KW - Symporters/genetics/physiology
KW - Transport Vesicles/metabolism
KW - Animals
KW - Humans
KW - Mice
KW - COS Cells
KW - Cercopithecus aethiops
KW - Cell Line, Tumor
KW - Hydrolysis
KW - Adaptor Proteins, Signal Transducing/genetics
KW - Nerve Tissue Proteins/metabolism
KW - Alzheimer Disease/enzymology/metabolism
KW - Amino Acid Transport Systems/genetics/physiology
KW - Amyloid Precursor Protein Secretases/metabolism
KW - Amyloid beta-Protein Precursor/biosynthesis/metabolism
KW - Protein Binding/genetics
KW - Protein Processing, Post-Translational/genetics
KW - Protein Transport/genetics
KW - Symporters/genetics/physiology
KW - Transport Vesicles/metabolism
M3 - SCORING: Journal article
VL - 281
SP - 40114
EP - 40123
JO - J BIOL CHEM
JF - J BIOL CHEM
SN - 0021-9258
IS - 52
M1 - 52
ER -
