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SORLA-Dependent and -Independent Functions for PACS1 in Control of Amyloidogenic Processes

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SORLA-Dependent and -Independent Functions for PACS1 in Control of Amyloidogenic Processes. / Burgert, Tilman; Schmidt, Vanessa; Caglayan, Safak; Lin, Fuyu; Füchtbauer, Annette; Füchtbauer, Ernst-Martin; Nykjaer, Anders; Carlo, Anne-Sophie; Willnow, Thomas E.

I: Molecular and Cellular Biology, Bind 33, Nr. 21, 03.09.2013, s. 4308-4320.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Burgert, T, Schmidt, V, Caglayan, S, Lin, F, Füchtbauer, A, Füchtbauer, E-M, Nykjaer, A, Carlo, A-S & Willnow, TE 2013, 'SORLA-Dependent and -Independent Functions for PACS1 in Control of Amyloidogenic Processes', Molecular and Cellular Biology, bind 33, nr. 21, s. 4308-4320. https://doi.org/10.1128/MCB.00628-13

APA

Burgert, T., Schmidt, V., Caglayan, S., Lin, F., Füchtbauer, A., Füchtbauer, E-M., Nykjaer, A., Carlo, A-S., & Willnow, T. E. (2013). SORLA-Dependent and -Independent Functions for PACS1 in Control of Amyloidogenic Processes. Molecular and Cellular Biology, 33(21), 4308-4320. https://doi.org/10.1128/MCB.00628-13

CBE

Burgert T, Schmidt V, Caglayan S, Lin F, Füchtbauer A, Füchtbauer E-M, Nykjaer A, Carlo A-S, Willnow TE. 2013. SORLA-Dependent and -Independent Functions for PACS1 in Control of Amyloidogenic Processes. Molecular and Cellular Biology. 33(21):4308-4320. https://doi.org/10.1128/MCB.00628-13

MLA

Vancouver

Burgert T, Schmidt V, Caglayan S, Lin F, Füchtbauer A, Füchtbauer E-M o.a. SORLA-Dependent and -Independent Functions for PACS1 in Control of Amyloidogenic Processes. Molecular and Cellular Biology. 2013 sep 3;33(21):4308-4320. https://doi.org/10.1128/MCB.00628-13

Author

Burgert, Tilman ; Schmidt, Vanessa ; Caglayan, Safak ; Lin, Fuyu ; Füchtbauer, Annette ; Füchtbauer, Ernst-Martin ; Nykjaer, Anders ; Carlo, Anne-Sophie ; Willnow, Thomas E. / SORLA-Dependent and -Independent Functions for PACS1 in Control of Amyloidogenic Processes. I: Molecular and Cellular Biology. 2013 ; Bind 33, Nr. 21. s. 4308-4320.

Bibtex

@article{9e0cd2b6869d4ccabf1936dfff13c79c,
title = "SORLA-Dependent and -Independent Functions for PACS1 in Control of Amyloidogenic Processes",
abstract = "Sorting-related receptor with A-type repeats (SORLA) is a sorting receptor for the amyloid precursor protein (APP) that prevents breakdown of APP into Aβ peptides, a hallmark of Alzheimer's disease (AD). Several cytosolic adaptors have been shown to interact with the cytoplasmic domain of SORLA, thereby controlling intracellular routing of SORLA/APP complexes in cell lines. However, the relevance of adaptor-mediated sorting of SORLA for amyloidogenic processes in vivo remained unexplored. We focused on the interaction of SORLA with phosphofurin acidic cluster sorting protein 1 (PACS1), an adaptor that shuttles proteins between the trans-Golgi network (TGN) and endosomes. By studying PACS1 knockdown in neuronal cell lines and investigating transgenic mice expressing a PACS1-binding-defective mutant form of SORLA, we found that disruption of SORLA and PACS1 interaction results in the inability of SORLA/APP complexes to sort to the TGN in neurons and in increased APP processing in the brain. Loss of PACS1 also impairs the proper expression of the cation-independent mannose 6-phosphate receptor and its target cathepsin B, a protease that breaks down Aβ. Thus, our data identified the importance of PACS1-dependent protein sorting for amyloidogenic-burden control via both SORLA-dependent and SORLA-independent mechanisms.",
author = "Tilman Burgert and Vanessa Schmidt and Safak Caglayan and Fuyu Lin and Annette F{\"u}chtbauer and Ernst-Martin F{\"u}chtbauer and Anders Nykjaer and Anne-Sophie Carlo and Willnow, {Thomas E}",
year = "2013",
month = sep,
day = "3",
doi = "10.1128/MCB.00628-13",
language = "English",
volume = "33",
pages = "4308--4320",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "21",

}

RIS

TY - JOUR

T1 - SORLA-Dependent and -Independent Functions for PACS1 in Control of Amyloidogenic Processes

AU - Burgert, Tilman

AU - Schmidt, Vanessa

AU - Caglayan, Safak

AU - Lin, Fuyu

AU - Füchtbauer, Annette

AU - Füchtbauer, Ernst-Martin

AU - Nykjaer, Anders

AU - Carlo, Anne-Sophie

AU - Willnow, Thomas E

PY - 2013/9/3

Y1 - 2013/9/3

N2 - Sorting-related receptor with A-type repeats (SORLA) is a sorting receptor for the amyloid precursor protein (APP) that prevents breakdown of APP into Aβ peptides, a hallmark of Alzheimer's disease (AD). Several cytosolic adaptors have been shown to interact with the cytoplasmic domain of SORLA, thereby controlling intracellular routing of SORLA/APP complexes in cell lines. However, the relevance of adaptor-mediated sorting of SORLA for amyloidogenic processes in vivo remained unexplored. We focused on the interaction of SORLA with phosphofurin acidic cluster sorting protein 1 (PACS1), an adaptor that shuttles proteins between the trans-Golgi network (TGN) and endosomes. By studying PACS1 knockdown in neuronal cell lines and investigating transgenic mice expressing a PACS1-binding-defective mutant form of SORLA, we found that disruption of SORLA and PACS1 interaction results in the inability of SORLA/APP complexes to sort to the TGN in neurons and in increased APP processing in the brain. Loss of PACS1 also impairs the proper expression of the cation-independent mannose 6-phosphate receptor and its target cathepsin B, a protease that breaks down Aβ. Thus, our data identified the importance of PACS1-dependent protein sorting for amyloidogenic-burden control via both SORLA-dependent and SORLA-independent mechanisms.

AB - Sorting-related receptor with A-type repeats (SORLA) is a sorting receptor for the amyloid precursor protein (APP) that prevents breakdown of APP into Aβ peptides, a hallmark of Alzheimer's disease (AD). Several cytosolic adaptors have been shown to interact with the cytoplasmic domain of SORLA, thereby controlling intracellular routing of SORLA/APP complexes in cell lines. However, the relevance of adaptor-mediated sorting of SORLA for amyloidogenic processes in vivo remained unexplored. We focused on the interaction of SORLA with phosphofurin acidic cluster sorting protein 1 (PACS1), an adaptor that shuttles proteins between the trans-Golgi network (TGN) and endosomes. By studying PACS1 knockdown in neuronal cell lines and investigating transgenic mice expressing a PACS1-binding-defective mutant form of SORLA, we found that disruption of SORLA and PACS1 interaction results in the inability of SORLA/APP complexes to sort to the TGN in neurons and in increased APP processing in the brain. Loss of PACS1 also impairs the proper expression of the cation-independent mannose 6-phosphate receptor and its target cathepsin B, a protease that breaks down Aβ. Thus, our data identified the importance of PACS1-dependent protein sorting for amyloidogenic-burden control via both SORLA-dependent and SORLA-independent mechanisms.

U2 - 10.1128/MCB.00628-13

DO - 10.1128/MCB.00628-13

M3 - Journal article

C2 - 24001769

VL - 33

SP - 4308

EP - 4320

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 21

ER -