title: Inositol deacylation by Bst1p is required for the quality control of glycosylphosphatidylinositol-anchored proteins.
abstract: Misfolded proteins are recognized in the endoplasmic reticulum (ER), transported back to the cytosol, and degraded by the proteasome. A number of proteins are processed and modified by a glycosylphosphatidylinositol (GPI) anchor in the ER, but the quality control mechanisms of GPI-anchored proteins remain unclear. Here, we report on the quality control mechanism of misfolded GPI-anchored proteins. We have constructed a mutant form of the beta-1,3-glucanosyltransferase Gas1p (Gas1*p) as a model misfolded GPI-anchored protein. Gas1*p was modified with a GPI anchor but retained in the ER and was degraded rapidly via the proteasome. Disruption of BST1, which encodes GPI inositol deacylase, caused a delay in the degradation of Gas1*p. This delay was because of an effect on the deacylation activity of Bst1p. Disruption of genes involved in GPI-anchored protein concentration and N-glycan processing caused different effects on the degradation of Gas1*p and a soluble misfolded version of carboxypeptidase Y. Furthermore, Gas1*p associated with both Bst1p and BiP/Kar2p, a molecular chaperone, in vivo. Our data suggest that GPI inositol deacylation plays important roles in the quality control and ER-associated degradation of GPI-anchored proteins.
authors.affiliation: Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan.
authors.forename: Morihisa
authors.initials: M
authors.lastname: Fujita
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yoko-O
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Jigami
mesh_terms: D000215:Acylation; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000502:physiology; D004693:Glucan Endo-1,3-beta-D-Glucosidase / Q000235:genetics; D006031:Glycosylation; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*
chemical_list: D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D050505:Mutant Proteins; D029701:Saccharomyces cerevisiae Proteins; D007294:Inositol; C509243:Bst1 protein, S cerevisiae; D010744:Phosphoric Monoester Hydrolases; C117939:1,3-beta-glucanosyltransferase; D004693:Glucan Endo-1,3-beta-D-Glucosidase; D046988:Proteasome Endopeptidase Complex