The 
-Glucuronidase Propeptide Contains a Serpin-related Octamer Necessary for Complex Formation with Egasyn Esterase and for Retention
within the Endoplasmic Reticulum (*)
- From the (1) Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263
- §To whom correspondence should be addressed: the Dept. of Molecular and Cellular Biology, Roswell Park Cancer Institute, Elm and Carlton Sts., Buffalo, NY 14263.
Abstract
β-Glucuronidase is retained within the endoplasmic reticulum (ER) via complex formation with esterase-22 (egasyn), which in turn has a COOH-terminal HTEL ER retention sequence. To identify the regions of glucuronidase that interact with egasyn, complex formation was assayed in COS cells cotransfected with egasyn cDNA and with either deletion constructs of glucuronidase or with constructs containing specific glucuronidase propeptide sequences appended to the carboxyl terminus of a rat secretory protein α1-acid glycoprotein. The region of glucuronidase essential for complex formation is a linear octamer sequence at the COOH terminus of the propeptide. A portion of this octamer is similar to a sequence near the reactive site of serpins. This and associated data indicate that an interaction related to that between serine proteinases and their serpin inhibitors retains β-glucuronidase within the ER. Further, attachment of this octamer sequence provides an alternative method of targeting proteins to the ER lumen of any cell that contains egasyn. These and related results demonstrate that complex formation with esterases/proteinases within the ER is important in the subcellular targeting and/or processing of certain proteins.
Footnotes
-
↵* This work was supported by Public Health Service Grant GM33559. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- ER
-
endoplasmic reticulum
- Gus
-
glucuronidase
- Man-6-P
-
mannose-6-phosphate
- AGP
-
α1-acid glycoprotein
- α1-AT
-
α1-antitrypsin
- WT
-
wild type
- PCR
-
polymerase chain reaction
- M bands
-
high molecular weight bands.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
