A novel role of CLPTM1 in the ER-associated degradation of membrane proteins

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The ER-associated degradation (ERAD) of various polytopic membrane proteins involves recognition of the polypeptide in the ER and its retrotranslocation into the cytosol, leading to its degradation by the proteasome system. The purpose of the present study was to unravel the role of CLPTM1 in the ERAD of an AE1 anion exchanger mutant, R664X AE1, with characteristic features of ubiquitin- and glycosylation-independence. In HEK293 cells expressing the AE1 mutant, CLPTM1 was localized in the ER and associated with several ER chaperone proteins including KIAA0090, p97/VCP, Derlins, and calnexin. However, overexpression or suppression of CLPTM1 had no apparent effect on proteasomal degradation of R664X AE1. In contrast, overexpression of KIAA0090 and/or p97/VCP accelerated the proteasomal degradation of the mutant.