Incorporation of desmocollin-2 into the plasma membrane requires N-glycosylation at multiple sites.

Brodehl A, Stanasiuk C, Anselmetti D, Gummert J, Milting H (2019)
FEBS open bio 9(4).

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Desmocollin-2 (DSC2) is a desmosomal protein of the cadherin family. Desmosomes are multiprotein complexes, which are involved in cell adhesion of cardiomyocytes and of keratinocytes. The molecular structure of the complete extracellular domain (ECD) of DSC2 was recently described, revealing three disulfide bridges, four N-glycosylation sites, and four O-mannosylation sites. However, the functional relevance of these post-translational modifications for the protein trafficking of DSC2 to the plasma membrane is still unknown. Here, we generated a set of DSC2 mutants, in which we systematically exchanged all N-glycosylation sites, O-mannosylation sites, and disulfide bridges within the ECD and investigated the resulting subcellular localization by confocal laser scanning microscopy. Of note, all single and double N-glycosylation- deficient mutants were efficiently incorporated into the plasma membrane, indicating that the absence of these glycosylation sites has a minor effect on the protein trafficking of DSC2. However, the exchange of multiple N-glycosylation sites resulted in intracellular accumulation. Colocalization analysis using cell compartment trackers revealed that N-glycosylation- deficient DSC2 mutants were retained within the Golgi apparatus. In contrast, elimination of the four O-mannosylation sites or the disulfide bridges in the ECD has no obvious effect on the intracellular protein processing of DSC2. These experiments underscore the importance of N-glycosylation at multiple sites of DSC2 for efficient intracellular transport to the plasma membrane. © 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
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Brodehl A, Stanasiuk C, Anselmetti D, Gummert J, Milting H. Incorporation of desmocollin-2 into the plasma membrane requires N-glycosylation at multiple sites. FEBS open bio. 2019;9(4).
Brodehl, A., Stanasiuk, C., Anselmetti, D., Gummert, J., & Milting, H. (2019). Incorporation of desmocollin-2 into the plasma membrane requires N-glycosylation at multiple sites. FEBS open bio, 9(4). doi:10.1002/2211-5463.12631
Brodehl, A., Stanasiuk, C., Anselmetti, D., Gummert, J., and Milting, H. (2019). Incorporation of desmocollin-2 into the plasma membrane requires N-glycosylation at multiple sites. FEBS open bio 9.
Brodehl, A., et al., 2019. Incorporation of desmocollin-2 into the plasma membrane requires N-glycosylation at multiple sites. FEBS open bio, 9(4).
A. Brodehl, et al., “Incorporation of desmocollin-2 into the plasma membrane requires N-glycosylation at multiple sites.”, FEBS open bio, vol. 9, 2019.
Brodehl, A., Stanasiuk, C., Anselmetti, D., Gummert, J., Milting, H.: Incorporation of desmocollin-2 into the plasma membrane requires N-glycosylation at multiple sites. FEBS open bio. 9, (2019).
Brodehl, Andreas, Stanasiuk, Caroline, Anselmetti, Dario, Gummert, Jan, and Milting, Hendrik. “Incorporation of desmocollin-2 into the plasma membrane requires N-glycosylation at multiple sites.”. FEBS open bio 9.4 (2019).

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