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PMID:21896273

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Citation

Behnke, J, Schneppenheim, J, Koch-Nolte, F, Haag, F, Saftig, P and Schröder, B (2011) Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes/late endosomes by a tyrosine motif in its C-terminal tail. FEBS Lett. 585:2951-7

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.

Links

PubMed Online version:10.1016/j.febslet.2011.08.043

Keywords

Amino Acid Motifs; Animals; Aspartic Acid Endopeptidases/chemistry; Aspartic Acid Endopeptidases/genetics; Aspartic Acid Endopeptidases/metabolism; Endosomes/metabolism; Fibroblasts/cytology; Fibroblasts/physiology; HeLa Cells; Humans; Lysosomes/metabolism; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mice; Molecular Sequence Data; Sequence Alignment; Tyrosine/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:LAMP2

located_in

GO:0005765: lysosomal membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:LAMP2

located_in

GO:0031902: late endosome membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:LAMP2

located_in

GO:0005765: lysosomal membrane

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000057)

Seeded From UniProt

complete

MOUSE:LAMP2

located_in

GO:0031902: late endosome membrane

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000057)

Seeded From UniProt

complete

HUMAN:SPP2B

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SPP2A

located_in

GO:0005765: lysosomal membrane

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000057)

Seeded From UniProt

complete

MOUSE:SPP2A

located_in

GO:0031902: late endosome membrane

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000057)

Seeded From UniProt

complete

MOUSE:LAMP2

part_of

GO:0005765: lysosomal membrane

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0000057)

Seeded From UniProt

complete

MOUSE:LAMP2

part_of

GO:0031902: late endosome membrane

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0000057)

Seeded From UniProt

complete


See also

References

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