The chemical chaperone sodium 4-phenylbutyrate improves the secretion of the protein CA267T mutant in CHO-K1 cells trough the GRASP55 pathway

Maria Eugenia Chollet; Ellen Skarpen; Nina Iversen; Per Morten Sandset; Grethe Skretting

doi:10.1186/s13578-015-0048-4

The chemical chaperone sodium 4-phenylbutyrate improves the secretion of the protein CA267T mutant in CHO-K1 cells trough the GRASP55 pathway

Cell Biosci. 2015 Oct 9:5:57. doi: 10.1186/s13578-015-0048-4. eCollection 2015.

Authors

Maria Eugenia Chollet¹, Ellen Skarpen², Nina Iversen³, Per Morten Sandset⁴, Grethe Skretting¹

Affiliations

¹ Department of Hematology, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway ; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Box 4950 Nydalen, 0424 Oslo, Norway.
² Core Facility for Advanced Light Microscopy, Institute for Cancer Research, Oslo University Hospital, Montebello, 0379 Oslo, Norway.
³ Department of Medical Genetics, Oslo University Hospital Ulleval, Oslo, Norway.
⁴ Department of Hematology, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway ; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Abstract

Some inherited coagulation factor deficiencies are caused by intracellular retention or degradation of misfolded proteins, and chemical chaperones have been shown to reverse protein misfolding. The purpose of the present study was to investigate whether chemical chaperones may improve secretion of the protein CA267T (PCA267T) mutant in a cellular model. Using stably transfected Chinese hamster ovary cells (CHO-K1) expressing PCA267T we demonstrate that sodium 4-phenylbutyrate (PBA) increased the secretion of PCA267T by approximately 4-fold in comparison with untreated cells, and that this secretion seemed to follow an unconventional pathway via the Golgi reassembly stacking protein (GRASP55).

Keywords: Chemical chaperones; GRASP55; Misfolding; Mutant; Protein C.