Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes/late endosomes by a tyrosine motif in its C-terminal tail
| Autor: | Paul Saftig, Janna Schneppenheim, Jörg Behnke, Bernd Schröder, Friedrich Koch-Nolte, Friedrich Haag |
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| Jazyk: | angličtina |
| Předmět: |
Lysosomal transport
Proteases Endosome Intramembrane protease Amino Acid Motifs Molecular Sequence Data Biophysics Endosomes Biology Biochemistry Regulated Intramembrane Proteolysis Mice Structural Biology Lysosome Genetics medicine SPPL2a Animals Aspartic Acid Endopeptidases Humans Tyrosine Molecular Biology Lysosomal targeting Membrane Proteins Cell Biology Fibroblasts Cell biology medicine.anatomical_structure Regulated intramembrane proteolysis biology.protein Tyrosine-based sorting motif Lysosomes Signal peptide peptidase Sequence Alignment HeLa Cells |
| Zdroj: | FEBS Letters. (19):2951-2957 |
| ISSN: | 0014-5793 |
| DOI: | 10.1016/j.febslet.2011.08.043 |
| Popis: | Signal-peptide-peptidase-like 2A (SPPL2a), an aspartyl intramembrane protease, has been implicated in the proteolysis of TNF-alpha, Fas Ligand and Bri2. Here, we show that endogenous SPPL2a – in agreement with overexpression studies – is localised in membranes of lysosomes/late endosomes. Furthermore, we have analysed the molecular determinants for lysosomal sorting of SPPL2a by creating chimaeric constructs between SPPL2a and its plasma membrane localised homologue SPPL2b. Lysosomal transport of SPPL2a critically depends on its cytosolic carboxyterminal tail. A canonical tyrosine-based sorting motif of the YXXø type at position 498 is sufficient to direct SPPL2a to lysosomal/late endosomal compartments. This motif accounts for the differential localisation of the homologous proteases SPPL2a and SPPL2b and thereby influences the access to substrates and biological function of SPPL2a.Structured summary of protein interactionsLAMP2 and SPPL2acolocalize by fluorescence microscopy(view interaction) |
| Databáze: | OpenAIRE |
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