Cytochromes P450 2C1/2 and P450 2E1 are retained in the endoplasmic reticulum membrane by different mechanisms

Elzbieta Szczesna-Skorupa, Ci Di Chen, Byron Kemper

Research output: Contribution to journalArticle

Abstract

Cytochrome P450 (P450) 2C1/2 contains redundant endoplasmic reticulum (ER) retention signals and is excluded from the recycling pathway. Other P450s, such as P450 2E1, have been detected in the plasma membrane and Golgi apparatus. To examine whether the mechanisms of ER retention might differ for P450 2C1/2 and P450 2E1, chimeras of green flourescent protein and the full- length proteins, N-terminal signal/anchor sequences, or the cytoplasmic catalytic domains from these proteins have been expressed in COS1 cells. Chimeras with either the N-terminal signal/anchor sequence or the cytoplasmic domain of P450 2C1/2 were retained in the ER and the distribution was not altered by treatment with nocodazole. A chimera with full-length P450 2E1 was located in the ER, but in contrast to P450 2C1/2, treatment with nocodazole resulted in redistribution to a vesicular pattern, which suggested that this protein was retained in the ER by a retrieval mechanism. In support of this possibility, the P450 2E1 chimera, but not the P450 2C1/2 chimera, was included in transport vesicles generated in an in vitro budding assay. A chimera with only the N-terminal signal/anchor sequence of P450 2E1 fused to green fluorescent protein was located in the ER and nocodazole treatment altered its distribution, whereas a chimera with only the cytoplasmic domain of P450 2E1 was not efficiently retained in the ER and accumulated primarily in the Golgi region. These results demonstrate that the mechanisms for retention in the ER of two closely related members of the P450 superfamily are different and that the N-terminal signal/anchor sequence contains the dominant retention signal. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)128-136
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume374
Issue number2
DOIs
StatePublished - Feb 15 2000

Keywords

  • Cytochrome P450
  • Endoplasmic reticulum
  • Targeting

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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