The Protein S Erlangen Mutation PROS1c.1904T>C (F635S) Suppresses Secretion.
Clin Lab
; 70(3)2024 Mar 01.
Article
en En
| MEDLINE
| ID: mdl-38469768
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trombosis
/
Proteína S
/
Deficiencia de Proteína S
/
Transporte de Proteínas
Límite:
Humans
Idioma:
En
Revista:
Clin Lab
Asunto de la revista:
TECNICAS E PROCEDIMENTOS DE LABORATORIO
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Alemania