Different motifs regulate trafficking of SorCS1 isoforms.
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Different motifs regulate trafficking of SorCS1 isoforms. / Nielsen, Morten S; Keat, Sady J; Hamati, Jida W; Madsen, Peder; Gutzmann, Jakob J; Engelsberg, Arne; Pedersen, Karen M; Gustafsen, Camilla; Nykjaer, Anders; Gliemann, Jørgen; Hermans-Borgmeyer, Irmgard; Kuhl, Dietmar; Petersen, Claus M; Hermey, Guido.
in: TRAFFIC, Jahrgang 9, Nr. 6, 6, 2008, S. 980-994.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Different motifs regulate trafficking of SorCS1 isoforms.
AU - Nielsen, Morten S
AU - Keat, Sady J
AU - Hamati, Jida W
AU - Madsen, Peder
AU - Gutzmann, Jakob J
AU - Engelsberg, Arne
AU - Pedersen, Karen M
AU - Gustafsen, Camilla
AU - Nykjaer, Anders
AU - Gliemann, Jørgen
AU - Hermans-Borgmeyer, Irmgard
AU - Kuhl, Dietmar
AU - Petersen, Claus M
AU - Hermey, Guido
PY - 2008
Y1 - 2008
N2 - The type I transmembrane protein SorCS1 is a member of the Vps10p-domain receptor family comprised of Sortilin, SorLA and SorCS1, -2 and -3. Current information indicates that Sortilin and SorLA mediate intracellular protein trafficking and sorting, but little is known about the cellular functions of the SorCS subgroup. SorCS1 binds platelet-derived growth factor-BB (PDGF-BB) and is expressed in isoforms differing only in their cytoplasmic domains. Here, we identify two novel isoforms of mouse SorCS1 designated m-SorCS1c and -d. In situ hybridization revealed a combinatorial expression pattern of the variants in brain and embryonic tissues. We demonstrate that among the mouse variants, only SorCS1c mediates internalization and that the highly conserved SorCS1c is internalized through a canonical tyrosine-based motif. In contrast, human SorCS1a, whose cytoplasmic domain is completely different from mouse SorCS1a, is internalized through a DXXLL motif. We report that the human SorCS1a cytoplasmic domain interacts with the alphaC/sigma2 subunits of the adaptor protein (AP)-2 complex, and internalization of human SorCS1a and -c is mediated by AP-2. Our results suggest that the endocytic isoforms target internalized cargo to lysosomes but are not engaged in Golgi-endosomal transport to a significant degree.
AB - The type I transmembrane protein SorCS1 is a member of the Vps10p-domain receptor family comprised of Sortilin, SorLA and SorCS1, -2 and -3. Current information indicates that Sortilin and SorLA mediate intracellular protein trafficking and sorting, but little is known about the cellular functions of the SorCS subgroup. SorCS1 binds platelet-derived growth factor-BB (PDGF-BB) and is expressed in isoforms differing only in their cytoplasmic domains. Here, we identify two novel isoforms of mouse SorCS1 designated m-SorCS1c and -d. In situ hybridization revealed a combinatorial expression pattern of the variants in brain and embryonic tissues. We demonstrate that among the mouse variants, only SorCS1c mediates internalization and that the highly conserved SorCS1c is internalized through a canonical tyrosine-based motif. In contrast, human SorCS1a, whose cytoplasmic domain is completely different from mouse SorCS1a, is internalized through a DXXLL motif. We report that the human SorCS1a cytoplasmic domain interacts with the alphaC/sigma2 subunits of the adaptor protein (AP)-2 complex, and internalization of human SorCS1a and -c is mediated by AP-2. Our results suggest that the endocytic isoforms target internalized cargo to lysosomes but are not engaged in Golgi-endosomal transport to a significant degree.
M3 - SCORING: Zeitschriftenaufsatz
VL - 9
SP - 980
EP - 994
JO - TRAFFIC
JF - TRAFFIC
SN - 1398-9219
IS - 6
M1 - 6
ER -
