Role of the membrane-proximal O-glycosylation site in sorting of the human receptor for neurotrophins to the apical membrane of MDCK cells - PubMed (original) (raw)

. 2002 Feb 15;273(2):178-86.

doi: 10.1006/excr.2001.5442.

Affiliations

• PMID: 11822873
• DOI: 10.1006/excr.2001.5442

Role of the membrane-proximal O-glycosylation site in sorting of the human receptor for neurotrophins to the apical membrane of MDCK cells

Lionel Breuza et al. Exp Cell Res. 2002.

Abstract

We have analyzed the respective roles of the stalk and/or the O-glycosylation sites in apical sorting by producing partially deleted mutants in this region of the human receptor for neurotrophins (P75(NTR)). The mere presence of O-glycosylations was not sufficient for efficient delivery to the apical surface since changing the stalk domain of P75(NTR) for the heavily O-glycosylated stalk from human decay-accelerating factor led to random distribution of the chimera. The presence of O-glycosylations, however, was a prerequisite for exit from the ER and protection from intracellular cleavage since a P75(NTR) containing the non O-glycosylated stalk of the human placental alkaline phosphatase was not transported to the cell surface but was cleaved and secreted from the basolateral side. Deletion of the membrane-proximal part of the stalk showed a more dramatic reversal of polarity of P75(NTR) than the deletion of the distal part. Furthermore, moving the first putative O-glycosylation site (T216) two amino acids away from the membrane resulted in a loss of apical polarity of P75(NTR), suggesting that an important clue for apical sorting resides in this part of the stalk. This loss of apical polarity paralleled a loss of association of P75(NTR) mutants with Lubrol rafts. These data indicate that the position of O-glycans in the proximal part of the stalk domain of P75(NTR) is crucial for apical sorting and may regulate association with apical rafts.

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