Sorting by the cytoplasmic domain of the amyloid precursor protein binding receptor SorLA.
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Sorting by the cytoplasmic domain of the amyloid precursor protein binding receptor SorLA. / Nielsen, Morten S; Gustafsen, Camilla; Madsen, Peder; Nyengaard, Jens R; Hermey, Guido; Bakke, Oddmund; Mari, Muriel; Schu, Peter; Pohlmann, Regina; Dennes, André; Petersen, Claus M.
In: MOL CELL BIOL, Vol. 27, No. 19, 19, 2007, p. 6842-6851.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Sorting by the cytoplasmic domain of the amyloid precursor protein binding receptor SorLA.
AU - Nielsen, Morten S
AU - Gustafsen, Camilla
AU - Madsen, Peder
AU - Nyengaard, Jens R
AU - Hermey, Guido
AU - Bakke, Oddmund
AU - Mari, Muriel
AU - Schu, Peter
AU - Pohlmann, Regina
AU - Dennes, André
AU - Petersen, Claus M
PY - 2007
Y1 - 2007
N2 - SorLA/LR11 (250 kDa) is the largest and most composite member of the Vps10p-domain receptors, a family of type 1 proteins preferentially expressed in neuronal tissue. SorLA binds several ligands, including neurotensin, platelet-derived growth factor-bb, and lipoprotein lipase, and via complex-formation with the amyloid precursor protein it downregulates generation of Alzheimer's disease-associated Abeta-peptide. The receptor is mainly located in vesicles, suggesting a function in protein sorting and transport. Here we examined SorLA's trafficking using full-length and chimeric receptors and find that its cytoplasmic tail mediates efficient Golgi body-endosome transport, as well as AP-2 complex-dependent endocytosis. Functional sorting sites were mapped to an acidic cluster-dileucine-like motif and to a GGA binding site in the C terminus. Experiments in permanently or transiently AP-1 mu1-chain-deficient cells established that the AP-1 adaptor complex is essential to SorLA's transport between Golgi membranes and endosomes. Our results further implicate the GGA proteins in SorLA trafficking and provide evidence that SNX1 and Vps35, as parts of the retromer complex or possibly in a separate context, are engaged in retraction of the receptor from endosomes.
AB - SorLA/LR11 (250 kDa) is the largest and most composite member of the Vps10p-domain receptors, a family of type 1 proteins preferentially expressed in neuronal tissue. SorLA binds several ligands, including neurotensin, platelet-derived growth factor-bb, and lipoprotein lipase, and via complex-formation with the amyloid precursor protein it downregulates generation of Alzheimer's disease-associated Abeta-peptide. The receptor is mainly located in vesicles, suggesting a function in protein sorting and transport. Here we examined SorLA's trafficking using full-length and chimeric receptors and find that its cytoplasmic tail mediates efficient Golgi body-endosome transport, as well as AP-2 complex-dependent endocytosis. Functional sorting sites were mapped to an acidic cluster-dileucine-like motif and to a GGA binding site in the C terminus. Experiments in permanently or transiently AP-1 mu1-chain-deficient cells established that the AP-1 adaptor complex is essential to SorLA's transport between Golgi membranes and endosomes. Our results further implicate the GGA proteins in SorLA trafficking and provide evidence that SNX1 and Vps35, as parts of the retromer complex or possibly in a separate context, are engaged in retraction of the receptor from endosomes.
M3 - SCORING: Zeitschriftenaufsatz
VL - 27
SP - 6842
EP - 6851
JO - MOL CELL BIOL
JF - MOL CELL BIOL
SN - 0270-7306
IS - 19
M1 - 19
ER -
