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Chondroitin Sulfate Accelerates Trans ‐Golgi‐to‐Surface Transport of Proteoglycan Amyloid Precursor Protein
Author(s) -
Mihov Deyan,
Raja Eva,
Spiess Martin
Publication year - 2015
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/tra.12294
Subject(s) - endosome , proteoglycan , chondroitin sulfate , microbiology and biotechnology , endocytosis , golgi apparatus , transport protein , perlecan , biology , intracellular , glycosaminoglycan , biochemistry , chemistry , cell , endoplasmic reticulum , extracellular matrix
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.