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- Title
The Protein S Erlangen Mutation PROS1<sub>c.1904T>C </sub>(F635S) Suppresses Secretion.
- Authors
Reißig, Julian; Cunningham, Sarah; Wandersee, Alexandra; Brox, Regine; Achenbach, Susanne; Strobel, Julian; Hackstein, Holger; Schneider, Sabine
- Abstract
Background: The recently identified PROS1 mutation Protein S Erlangen c.1904T>C, resulting in amino acid exchange F635S, is associated with severe quantitative protein S (PS) deficiency and clinical thrombosis. It was hypothesized that this deficiency is due to a secretion defect [1]. This report aims to further elucidate the potential secretion defect of PS Erlangen. Methods: Coding sequences (CDS) of wild type (WT) PROS1 (encoding PS) and mutated PROS1c.1904T>C (encoding PSF635S) were cloned in front of the CDS of green fluorescent protein (GFP), and the respective plasmids were introduced into HEK293T cells. PROS1-GFP and PROS1c.1904T>C-GFP expressing HEK293T cell lines were analyzed by confocal laser scanning microscopy and western blot for cellular proteins and proteins secreted to the growth medium. Results: Western blot analysis revealed a significantly reduced secretion of PSF635S compared to WT PS. This observation was confirmed by the detection of mutant PSF635S-GFP fusion exclusively in the endoplasmic reticulum (ER), while PS-GFP passed through the entire secretory pathway, as indicated by the localization within both the ER and Golgi apparatus. Conclusions: The Protein S Erlangen mutation results in type I PS deficiency caused by a secretion defect.
- Subjects
PROTEIN S; GOLGI apparatus; GREEN fluorescent protein; SECRETION; WESTERN immunoblotting; PROTEIN S deficiency
- Publication
Clinical Laboratory, 2024, Vol 70, Issue 3, p525
- ISSN
1433-6510
- Publication type
Article
- DOI
10.7754/Clin.Lab.2023.230906