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Chondroitin Sulfate Accelerates Trans-Golgi-to-Surface Transport of Proteoglycan Amyloid Precursor Protein

Mihov, Deyan and Raja, Eva and Spiess, Martin. (2015) Chondroitin Sulfate Accelerates Trans-Golgi-to-Surface Transport of Proteoglycan Amyloid Precursor Protein. Traffic, Vol. 16, H. 8. pp. 853-870.

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Official URL: http://edoc.unibas.ch/dok/A6411096

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Abstract

The amyloid precursor protein (APP) is a membrane protein implicated in the pathogenesis of Alzheimer's disease. APP is a part-time proteoglycan, as splice variants lacking exon 15 are modified by a chondroitin sulfate glycosaminoglycan (GAG) chain. Investigating the effect of the GAG chain on the trafficking of APP in non-polarized cells, we found it to increase the steady-state surface-to-intracellular distribution, to reduce the rate of endocytosis and to accelerate transport kinetics from the trans-Golgi network (TGN) to the plasma membrane. Deletion of the cytosolic domain resulted in delayed surface arrival of GAG-free APP, but did not affect the rapid export kinetics of the proteoglycan form. Protein-free GAG chains showed the same TGN-to-cell surface transport kinetics as proteoglycan APP. Endosome ablation experiments were performed to distinguish between indirect endosomal and direct pathways to the cell surface. Surprisingly, TGN-to-cell surface transport of both GAG-free and proteoglycan APP was found to be indirect via transferrin-positive endosomes. Our results show that GAGs act as alternative sorting determinants in cellular APP transport that are dominant over cytoplasmic signals and involve distinct sorting mechanisms.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Spiess)
UniBasel Contributors:Spiess, Martin
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Blackwell
ISSN:1398-9219
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:04 Sep 2015 14:30
Deposited On:04 Sep 2015 14:30

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