In Vivo Force Measurements Reveal that GSK-3 Regulates Axonal Transport by Altering the Number of Active Motors
| Autor: | Nicole M. Farley, Lawrence S.B. Goldstein, Lukasz Szpankowski, George T. Shubeita, Christina Leidel, Carole Weaver |
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| Rok vydání: | 2012 |
| Předmět: |
0303 health sciences
biology Dynein Biophysics macromolecular substances 010402 general chemistry 01 natural sciences 0104 chemical sciences Cell biology Motor protein 03 medical and health sciences medicine.anatomical_structure nervous system Microtubule GSK-3 In vivo medicine Amyloid precursor protein biology.protein Axoplasmic transport Axon 030304 developmental biology |
| Zdroj: | Biophysical Journal. 102(3) |
| ISSN: | 0006-3495 |
| DOI: | 10.1016/j.bpj.2011.11.2077 |
| Popis: | Neurons rely on microtubule motor proteins such as kinesin-1 and dynein to transport essential cargos along the axon. Defective transport is connected to neurodegenerative diseases, including Alzheimer's disease. Glycogen Synthase Kinase 3(GSK-3) has been proposed to be a central player in Alzheimer's. We show that GSK-3 is a required negative regulator of both kinesin-1-mediated and dynein-mediated transport of the Amyloid Precursor Protein, a key contributor to Alzheimer's pathology. By measuring the forces motors generate in vivo, we find that GSK-3 regulates transport by altering the activity of kinesin-1 motors but not their binding to the cargo leading us to propose that this regulation occurs via a mechanism of changing motor-microtubule interactions. |
| Databáze: | OpenAIRE |
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