Fig. 4: ER retention and activation of ER stress/UPR by mutant COMP.
From: Mutations in COMP cause familial carpal tunnel syndrome
a Wild-type, V66E, and R718W mutant COMP were expressed in primary tendon cells or RCS cells. Cell lysates and culture medium were respectively collected. Immunoblotting results indicate poor secretion of V66E mutant COMP by primary tendon cells but not RCS cells. The secretion of R718W-COMP is impaired in both types of cells. RCS rat chondrosarcoma cells, FBN fibronectin. The secretion ratios of different COMP from three experiments are quantified and summarized in the right panel, two-tailed t test, ***p = 0.00095 (V66E) and *p = 0.0161 (R718W) for primary tendon cells, p = 0.107 (V66E) and *p = 0.0108 (R718W) for RCS cells, error bars are ± SEM. b–d Normal (n = 2) and Family 1 patients’ TCL tissues (n = 3) were analyzed. b Immunofluorescent staining indicates strong co-localization of COMP (green) and endoplasmic reticulum (ER, recognized by KDEL antibody, red) in patients’ TCL cells. DAPI stains cell nucleus (blue). c Transmission electron microscopy (TEM) shows distended and fragmented ER in CTS patients’ TCL cells (red arrows). d Immunohistochemical staining shows upregulation of BIP, ATF4, and CHOP in patients’ TCLs, indicating activation of ER stress/unfolded protein response (UPR) in CTS patients. Arrows point to the perinuclear staining of the ER-resident BIP. The boxed areas (black box) in the figures are magnified and shown in the insets (white box). Source data are provided as a Source Data file.
