Stomatin-like Protein-1 Interacts with Stomatin and Is Targeted to Late Endosomes: SLP-1 Is a Late Endosomal Membrane Protein

Mario Mairhofer, Marianne Steiner, Ulrich Salzer, Rainer Prohaska

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

The human stomatin-like protein-1 (SLP-1) is a membrane protein with a characteristic bipartite structure containing a stomatin domain and a sterol carrier protein-2 (SCP-2) domain. This structure suggests a role for SLP-1 in sterol/lipid transfer and transport. Because SLP-1 has not been investigated, we first studied the molecular and cell biological characteristics of the expressed protein. We show here that SLP-1 localizes to the late endosomal compartment, like stomatin. Unlike stomatin, SLP-1 does not localize to the plasma membrane. Overexpression of SLP-1 leads to the redistribution of stomatin from the plasma membrane to late endosomes suggesting a complex formation between these proteins. We found that the targeting of SLP-1 to late endosomes is caused by a GYXXΦ (Φ being a bulky, hydrophobic amino acid) sorting signal at the N terminus. Mutation of this signal results in plasma membrane localization. SLP-1 and stomatin co-localize in the late endosomal compartment, they co-immunoprecipitate, thus showing a direct interaction, and they associate with detergent-resistant membranes. In accordance with the proposed lipid transfer function, we show that, under conditions of blocked cholesterol efflux from late endosomes, SLP-1 induces the formation of enlarged, cholesterol-filled, weakly LAMP-2-positive, acidic vesicles in the perinuclear region. This massive cholesterol accumulation clearly depends on the SCP-2 domain of SLP-1, suggesting a role for this domain in cholesterol transfer to late endosomes.
Original languageEnglish
Pages (from-to)29218-29229
Number of pages12
JournalJournal of Biological Chemistry
Volume284
Issue number42
DOIs
Publication statusPublished - 16 Oct 2009

Keywords

  • SLP1
  • stomatin
  • late endosome
  • lipid raft
  • cholesterol transport
  • Protein Structure, Tertiary
  • rab GTP-Binding Proteins/chemistry
  • Cholesterol/chemistry
  • Humans
  • Molecular Sequence Data
  • Lysosomes/metabolism
  • Nerve Tissue Proteins
  • Endosomes/chemistry
  • Animals
  • Membrane Proteins/chemistry
  • Models, Biological
  • Base Sequence
  • Cell Membrane/metabolism
  • Dogs
  • Protein Binding
  • HeLa Cells

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