Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta
Fig 4
TRIC-B deficiency activates ER stress.
(A) Immunoblots of steady-state cell lysates demonstrate equivalent levels of ATF6 (N, nuclear form) protein in proband (P1, P2, P3) versus normal control cells. Increased ATF4 protein in proband cells is consistent with activation of the PERK pathway of the UPR, and is similar to the increase in normal control fibroblasts treated with the SERCA inhibitor thapsigargin (THAP), but in contrast to normal control cells treated with N-glycosylation inhibitor tunicamycin (TUNI). (B) RT-PCR amplification of XBP1 mRNA from normal control and proband (P1, P2, P3) cells. There is no difference in the ratio of spliced (XBP-1s) to unspliced (XBP-1u) transcripts between control and proband cells, while partial and complete splicing are detected in normal control fibroblasts treated with tunicamycin (TUNI) and thapsigargin (THAP), respectively.