Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes/late endosomes by a tyrosine motif in its C-terminal tail.
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Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes/late endosomes by a tyrosine motif in its C-terminal tail. / Behnke, Jörg; Schneppenheim, Janna; Koch Nolte, Friedrich; Haag, Friedrich; Saftig, Paul; Schröder, Bernd.
In: FEBS LETT, Vol. 585, No. 19, 19, 2011, p. 2951-2957.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes/late endosomes by a tyrosine motif in its C-terminal tail.
AU - Behnke, Jörg
AU - Schneppenheim, Janna
AU - Koch Nolte, Friedrich
AU - Haag, Friedrich
AU - Saftig, Paul
AU - Schröder, Bernd
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Animals
KW - Humans
KW - Mice
KW - Molecular Sequence Data
KW - Sequence Alignment
KW - Hela Cells
KW - Amino Acid Motifs
KW - Aspartic Acid Endopeptidases/chemistry/genetics/metabolism
KW - Endosomes/metabolism
KW - Fibroblasts/cytology/physiology
KW - Lysosomes/metabolism
KW - Membrane Proteins/genetics/metabolism
KW - Tyrosine/metabolism
KW - Animals
KW - Humans
KW - Mice
KW - Molecular Sequence Data
KW - Sequence Alignment
KW - Hela Cells
KW - Amino Acid Motifs
KW - Aspartic Acid Endopeptidases/chemistry/genetics/metabolism
KW - Endosomes/metabolism
KW - Fibroblasts/cytology/physiology
KW - Lysosomes/metabolism
KW - Membrane Proteins/genetics/metabolism
KW - Tyrosine/metabolism
M3 - SCORING: Journal article
VL - 585
SP - 2951
EP - 2957
JO - FEBS LETT
JF - FEBS LETT
SN - 0014-5793
IS - 19
M1 - 19
ER -