Stomatin-like protein-1 interacts with stomatin and is targeted to late endosomes.
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 GYXXPhi (Phi 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.
Mairhofer
Mario
M
Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University of Vienna, Vienna A-1030, Austria.
Steiner
Marianne
M
Salzer
Ulrich
U
Prohaska
Rainer
R
D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry; D004285:Dogs; D011992:Endosomes / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020691:rab GTP-Binding Proteins / Q000737:chemistry
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C117201:STOML1 protein, human; D002784:Cholesterol; D020691:rab GTP-Binding Proteins
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