title: Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes/late endosomes by a tyrosine motif in its C-terminal tail.
abstract: 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.
authors: Biochemical Institute, Christian-Albrechts-University Kiel, Kiel, Germany.
authors: Jörg
authors: J
authors: Behnke
authors: Janna
authors: J
authors: Schneppenheim
authors: Friedrich
authors: F
authors: Koch-Nolte
authors: Friedrich
authors: F
authors: Haag
authors: Paul
authors: P
authors: Saftig
authors: Bernd
authors: B
authors: Schröder
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D014443:Tyrosine; D016282:Aspartic Acid Endopeptidases; C524670:SPPL2a protein, human; C568855:SPPL2a protein, mouse; C526456:SPPL2b protein, human; C568856:SPPL2b protein, mouse