Erlin-1 and erlin-2 are novel members of the prohibitin family of proteins that define lipid-raft-like domains of the ER

J Cell Sci. 2006 Aug 1;119(Pt 15):3149-60. doi: 10.1242/jcs.03060. Epub 2006 Jul 11.

Abstract

Our laboratory was interested in characterizing the molecular composition of non-caveolar lipid rafts. Thus, we generated monoclonal antibodies to lipid raft proteins of human myelomonocytic cells. Two of these proteins, KE04p and C8orf2, were found to be highly enriched in the detergent-insoluble, buoyant fraction of sucrose gradients in a cholesterol-dependent manner. They contain an evolutionarily conserved domain placing them in the prohibitin family of proteins. In contrast to other family members, these two proteins localized to the ER. Furthermore, the extreme N-termini of KE04p and C8orf2 were found to be sufficient for heterologous targeting of GFP to the ER in the absence of classical ER retrieval motifs. We also demonstrate that all prohibitin family members rely on sequences in their extreme N-termini for their distinctive subcellular distributions including the mitochondria, plasma membrane and Golgi vesicles. Owing to their subcellular localization and their presence in lipid rafts, we have named KE04p and C8orf2, ER lipid raft protein (erlin)-1 and erlin-2, respectively. Interestingly, the ER contains relatively low levels of cholesterol and sphingolipids compared with other organelles. Thus, our data support the existence of lipid-raft-like domains within the membranes of the ER.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cholesterol / metabolism
  • Endoplasmic Reticulum / chemistry
  • Endoplasmic Reticulum / metabolism*
  • Humans
  • Membrane Microdomains / chemistry
  • Membrane Microdomains / metabolism*
  • Membrane Proteins / classification
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Monocytes / chemistry
  • Monocytes / cytology
  • Monocytes / metabolism
  • Nerve Tissue Proteins / classification
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Phylogeny
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Sequence Alignment
  • Subcellular Fractions / chemistry
  • Subcellular Fractions / metabolism

Substances

  • ERLIN1 protein, human
  • ERLIN2 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • STOM protein, human
  • flotillins
  • prohibitin
  • Cholesterol