LRP1 modulates APP trafficking along early compartments of the secretory pathway
The amyloid beta peptide (Aβ) is a central player in Alzheimer's disease (AD) pathology. Aβ liberation depends on APP cleavage by β- and γ-secretases. The low density lipoprotein receptor related protein 1 (LRP1) was shown to mediate APP processing at multiple steps. Newly synthesized LRP1 can...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2008-08-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996108000739 |
| _version_ | 1818721799323516928 |
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| author | Elaine Waldron Catherine Heilig Andrea Schweitzer Nirupa Nadella Sebastian Jaeger Anne M. Martin Sascha Weggen Klaudia Brix Claus U. Pietrzik |
| author_facet | Elaine Waldron Catherine Heilig Andrea Schweitzer Nirupa Nadella Sebastian Jaeger Anne M. Martin Sascha Weggen Klaudia Brix Claus U. Pietrzik |
| author_sort | Elaine Waldron |
| collection | DOAJ |
| description | The amyloid beta peptide (Aβ) is a central player in Alzheimer's disease (AD) pathology. Aβ liberation depends on APP cleavage by β- and γ-secretases. The low density lipoprotein receptor related protein 1 (LRP1) was shown to mediate APP processing at multiple steps. Newly synthesized LRP1 can interact with APP, implying an interaction between these two proteins early in the secretory pathway. We wanted to investigate whether LRP1 mediates APP trafficking along the secretory pathway, and, if so, whether it affects APP processing. Indeed, the early trafficking of APP within the secretory pathway is strongly influenced by its interaction with the C-terminal domain of LRP1. The LRP1-construct expressing an ER-retention motif, LRP-CT KKAA, had the capacity to retard APP traffic to early secretory compartments. In addition, we provide evidence that APP metabolism occurs in close conjunction with LRP1 trafficking, highlighting a new role of lipoprotein receptors in neurodegenerative diseases. |
| first_indexed | 2024-12-17T20:44:28Z |
| format | Article |
| id | doaj.art-6c536fc471564a85b28407ca26a72aa0 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T20:44:28Z |
| publishDate | 2008-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-6c536fc471564a85b28407ca26a72aa02022-12-21T21:33:12ZengElsevierNeurobiology of Disease1095-953X2008-08-01312188197LRP1 modulates APP trafficking along early compartments of the secretory pathwayElaine Waldron0Catherine Heilig1Andrea Schweitzer2Nirupa Nadella3Sebastian Jaeger4Anne M. Martin5Sascha Weggen6Klaudia Brix7Claus U. Pietrzik8Institute of Physiological Chemistry and Pathobiochemistry, Molecular Neurodegeneration, Johannes Gutenberg-University Mainz, 55099 Mainz, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, Molecular Neurodegeneration, Johannes Gutenberg-University Mainz, 55099 Mainz, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, Molecular Neurodegeneration, Johannes Gutenberg-University Mainz, 55099 Mainz, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, Molecular Neurodegeneration, Johannes Gutenberg-University Mainz, 55099 Mainz, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, Molecular Neurodegeneration, Johannes Gutenberg-University Mainz, 55099 Mainz, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, Molecular Neurodegeneration, Johannes Gutenberg-University Mainz, 55099 Mainz, GermanyDepartment of Neuropathology, Heinrich-Heine-University, 40225 Düsseldorf, GermanySchool of Engineering and Science, Jacobs University Bremen, 28759 Bremen, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, Molecular Neurodegeneration, Johannes Gutenberg-University Mainz, 55099 Mainz, Germany; Corresponding author. Fax: +49 6131 3926488.The amyloid beta peptide (Aβ) is a central player in Alzheimer's disease (AD) pathology. Aβ liberation depends on APP cleavage by β- and γ-secretases. The low density lipoprotein receptor related protein 1 (LRP1) was shown to mediate APP processing at multiple steps. Newly synthesized LRP1 can interact with APP, implying an interaction between these two proteins early in the secretory pathway. We wanted to investigate whether LRP1 mediates APP trafficking along the secretory pathway, and, if so, whether it affects APP processing. Indeed, the early trafficking of APP within the secretory pathway is strongly influenced by its interaction with the C-terminal domain of LRP1. The LRP1-construct expressing an ER-retention motif, LRP-CT KKAA, had the capacity to retard APP traffic to early secretory compartments. In addition, we provide evidence that APP metabolism occurs in close conjunction with LRP1 trafficking, highlighting a new role of lipoprotein receptors in neurodegenerative diseases.http://www.sciencedirect.com/science/article/pii/S0969996108000739Low density lipoprotein receptor related proteinAmyloid precursor proteinTrafficingSecretory pathwayRetention |
| spellingShingle | Elaine Waldron Catherine Heilig Andrea Schweitzer Nirupa Nadella Sebastian Jaeger Anne M. Martin Sascha Weggen Klaudia Brix Claus U. Pietrzik LRP1 modulates APP trafficking along early compartments of the secretory pathway Neurobiology of Disease Low density lipoprotein receptor related protein Amyloid precursor protein Trafficing Secretory pathway Retention |
| title | LRP1 modulates APP trafficking along early compartments of the secretory pathway |
| title_full | LRP1 modulates APP trafficking along early compartments of the secretory pathway |
| title_fullStr | LRP1 modulates APP trafficking along early compartments of the secretory pathway |
| title_full_unstemmed | LRP1 modulates APP trafficking along early compartments of the secretory pathway |
| title_short | LRP1 modulates APP trafficking along early compartments of the secretory pathway |
| title_sort | lrp1 modulates app trafficking along early compartments of the secretory pathway |
| topic | Low density lipoprotein receptor related protein Amyloid precursor protein Trafficing Secretory pathway Retention |
| url | http://www.sciencedirect.com/science/article/pii/S0969996108000739 |
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