Proteomic analysis of the secretome of chondrocyte-like cells in Saul-Wilson syndrome

ABSTRACT: Saul-Wilson syndrome (SWS) is a rare skeletal dysplasia often presents with features such as a distinct facial phenotype, cataracts, short stature, clubfoot deformities, and microcephaly. We have previously identified that the causative mutation in SWS is a heterozygous, dominant variant (p.G516R) in COG4. COG4 is a Golgi-associated protein which plays important roles in protein trafficking. We further showed that the mutation impacts glycosylation of proteoglycans and disturbs chondrocyte elongation and intercalation in zebrafish embryos expressing COG4p.G516R variant. These effects could be partially rescued by adding wild type cells or their conditioned medium, implicating secretion anomalies associated with COG4p.G516R variant. We have conducted proteomic analysis of the conditioned medium from chondrocyte-like cells (SW1353) expressing COG4p.G516R variant and compared these to wild type SW1353 cells and a knockout of COG4 in these cells. 4,4438 proteins were identified and quantified and comparative analysis was performed. We utilized 3D cultures for performing secretome analysis to investigate the specific changes caused by p.G516R variant compared to WT and COG4-KO.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Saul-wilson Syndrome

SUBMITTER: Hudson Freeze  

LAB HEAD: Hudson Freeze

PROVIDER: PXD036151 | Pride | 2023-03-11

REPOSITORIES: Pride