Sensing of nutrients by CPT1C regulates late endosome/lysosome anterograde transport and axon growth

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...

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Detalles Bibliográficos
Autores: Palomo-Guerrero, Marta, Fadó Andrés, Rut, Casas, Maria, Pérez-Montero, Marta, Baena Muñoz, Miguel, Helmer, Patrick O, Domínguez, José Luis, Roig, Aina, Serra i Cucurull, Dolors, Hayen, Heiko, Stenmark, Harald, Raiborg, Camilla, Casals, Núria
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/152738
Acceso en línea:https://hdl.handle.net/2445/152738
Access Level:acceso abierto
Palabra clave:Carnitina palmitoïl-transferasa 1
Axons
Lisosomes
Carnitine palmitoyltransferase I
Lysosomes
Descripción
Sumario: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.

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