M-LP, Mpv17-like protein, has a peroxisomal membrane targeting signal comprising a transmembrane domain and a positively charged loop and up-regulates expression of the manganese superoxide dismutase gene

J Biol Chem. 2003 Feb 21;278(8):6301-6. doi: 10.1074/jbc.M210886200. Epub 2002 Dec 5.

Abstract

M-LP (Mpv17-like protein) has been identified as a new protein that has high sequence homology with Mpv17 protein, a peroxisomal membrane protein involved in the development of early onset glomerulosclerosis. In this study, we verified the peroxisomal localization of M-LP by performing dual-color confocal analysis of COS-7 cells cotransfected with green fluorescent protein-tagged M-LP and DsRED2-PTS1, a red fluorescent peroxisomal marker. To characterize the peroxisomal membrane targeting signal, we examined the intracellular localizations of several green fluorescent protein-tagged deletion mutants and demonstrated that, of the three transmembrane segments predicted, the first near the NH(2) terminus and NH(2)-terminal half of the following loop region, which is abundant in positively charged amino acids, were necessary and sufficient for peroxisomal targeting. To elucidate the function of M-LP, we examined the activities of several enzymes involved in reactive oxygen species metabolism in COS-7 cells and found that transfection with M-LP increased the superoxide dismutase activity significantly. Quantitative real-time PCR analysis revealed that the manganese SOD (SOD2) mRNA level of COS-7 cells transfected with M-LP was elevated. These results indicate that M-LP participates in reactive oxygen species metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • Animals
  • Base Sequence
  • COS Cells
  • Chlorocebus aethiops
  • DNA Primers
  • Gene Expression Regulation, Enzymologic*
  • Genes, Reporter
  • Genetic Vectors
  • Intracellular Membranes / physiology*
  • Kidney / metabolism
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism*
  • Mice
  • Peroxisomes / physiology*
  • Polymerase Chain Reaction
  • Protein Structure, Secondary
  • RNA, Messenger / genetics
  • Reactive Oxygen Species / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Superoxide Dismutase / genetics*
  • Transcription, Genetic
  • Transfection

Substances

  • 5' Untranslated Regions
  • DNA Primers
  • Membrane Proteins
  • Mpv17l protein, mouse
  • RNA, Messenger
  • Reactive Oxygen Species
  • Recombinant Fusion Proteins
  • Superoxide Dismutase