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Vol. 17, Issue 2, 834-850, February 2006

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Inositol Deacylation by Bst1p Is Required for the Quality Control of Glycosylphosphatidylinositol-anchored Proteins

Morihisa Fujita ^* , Takehiko Yoko-o ^*, and Yoshifumi Jigami ^* 

^* Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan; Graduate School of Life and Environmental Science, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan

Submitted May 20, 2005; Accepted November 15, 2005
Monitoring Editor: Jeffrey Brodsky

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 -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.

Abbreviations used: CHX, cycloheximide; CPY, carboxypeptidase Y; ER, endoplasmic reticulum; ERAD, endoplasmic reticulum-associated degradation; GPI, glycosylphosphatidylinositol; HRP, horseradish peroxidase; mRFP, monomeric red fluorescent protein.

Address correspondence to: Yoshifumi Jigami (jigami.yoshi{at}aist.go.jp).

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