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Bap31 Enhances the Endoplasmic Reticulum Export and Quality Control of Human Class I MHC Molecules¹

John J. Ladasky^*, Sarah Boyle^*, Malini Seth^2,*, Hewang Li^3,*, Tsvetelina Pentcheva^4,*, Fumiyoshi Abe^5,*, Steven J. Steinberg and Michael Edidin^6,*

^* Department of Biology, Johns Hopkins University, Baltimore, MD 21218; and Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205

The assembly of class I MHC molecules and their export from the endoplasmic reticulum (ER) is governed by chaperones and accessory proteins. We present evidence that the putative cargo receptor protein Bap31 participates in the transport and the quality control of human class I molecules. Transfection of the human adenocarcinoma cell line HeLa with yellow fluorescent protein-Bap31 chimeras increased surface levels of class I in a dose-dependent manner, by as much as 3.7-fold. The increase in surface class I resulted from an increase in the rate of export of newly synthesized class I molecules to the cell surface and from an increase in the stability of the exported molecules. We propose that Bap31 performs quality control on class I molecules in two distinct phases: first, by exporting peptide-loaded class I molecules to the ER/Golgi intermediate compartment, and second, by retrieving class I molecules that have lost peptides in the acidic post-ER environment. This function of Bap31 is conditional or redundant, because we find that Bap31 deficiency does not reduce surface class I levels. Overexpression of the Bap31 homolog, Bap29, decreases surface class levels in HeLa, indicating that it does not substitute for Bap31.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant AI-14584 (to M.E.). J.J.L. was supported in part by Training Grant T32AI007247 (Mark Soloski, principal investigator).

² Current address: Department of Medicine, Duke University Medical Center, Durham, NC 27701.

³ Current address: Department of Pediatrics, Georgetown University Medical Center, Washington, DC 20007.

⁴ Current address: Memorial Sloan-Kettering Cancer Center, New York, NY 10021.

⁵ Current address: Japan Agency for Marine-Earth Science and Technology, Yokosuka 237-0061, Japan.

⁶ Address correspondence and reprint requests to Dr. Michael Edidin, Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218. E-mail address: edidin{at}jhu.edu

⁷ Abbreviations used in this paper: ER, endoplasmic reticulum; ERGIC, ER/Golgi intermediate compartment; CFTR, cystic fibrosis transmembrane conductance regulator; CADDS, contiguous X-linked adrenoleukodystrophy/DXS1357E deletion syndrome; X-ALD, X-linked adrenoleukodystrophy; siRNA, small interfering RNA; EGFP, enhanced GFP; YFP, yellow fluorescent protein; CFP, cyan fluorescent protein.

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