Sensing of nutrients by CPT1C regulates late endosome/lysosome anterograde transport and axon growth
| Autor: | Rut Fadó, Núria Casals, José L. Domínguez, Camilla Raiborg, Miguel Baena, Aina Roig, Dolors Serra, Marta Palomo-Guerrero, Patrick O. Helmer, Harald Stenmark, Heiko Hayen, Maria Casas, Marta Pérez-Montero |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Mouse Ratones carnitine palmitoyltransferase 1C Kinesins Àcids grassos Neurones late endosome/lysosome Neuronas Mice 0302 clinical medicine AMP-Activated Protein Kinase Kinases Axon terminal malonyl-CoA axon growth Neurociències Ratolins Axon Biology (General) Late endosome Ácidos grasos Neurons Chemistry General Neuroscience Carnitina palmitoïl-transferasa 1 Brain General Medicine Cell biology Malonyl Coenzyme A anterograde transport medicine.anatomical_structure Medicine Research Article Human Lisosomes Endosome QH301-705.5 Science Neurociencias Citologia Endosomes General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Axiomas Citología Lysosome medicine Animals Humans Fatty acids Carnitine O-Palmitoyltransferase General Immunology and Microbiology energy stress Endoplasmic reticulum Neurosciences AMPK Biological Transport Nutrients Cell Biology Axons 030104 developmental biology Glucose Glucosa Axoplasmic transport Carnitine palmitoyltransferase I Cytology Lysosomes Protein Kinases 030217 neurology & neurosurgery Lisosomas HeLa Cells Neuroscience |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Recercat: Dipósit de la Recerca de Catalunya Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) eLife eLife, Vol 8 (2019) Recercat. Dipósit de la Recerca de Catalunya instname |
| ISSN: | 2050-084X |
| Popis: | Anterograde transport of late endosomes or lysosomes (LE/Lys) is crucial for proper axon growth. However, the role of energetic nutrients has been poorly explored. Malonyl-CoA is a precursor of fatty acids, and its intracellular levels highly fluctuate depending on glucose availability or the energy sensor AMP-activated protein kinase (AMPK). We demonstrate in HeLa cells that carnitine palmitoyltransferase 1C (CPT1C) senses malonyl-CoA and enhances LE/Lys anterograde transport by interacting with the endoplasmic reticulum protein protrudin and facilitating the transfer of Kinesin-1 from protrudin to LE/Lys. In cultured mouse cortical neurons, glucose deprivation, pharmacological activation of AMPK or inhibition of malonyl-CoA synthesis decreases LE/Lys abundance at the axon terminal, and shortens axon length in a CPT1C-dependent manner. These results identify CPT1C as a new regulator of anterograde LE/Lys transport in response to malonyl-CoA changes, and give insight into how axon growth is controlled by nutrients. info:eu-repo/semantics/acceptedVersion |
| Databáze: | OpenAIRE |
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