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Title: Sensing of nutrients by CPT1C regulates late endosome/lysosome anterograde transport and axon growth
Author: Palomo-Guerrero, Marta
Fadó, 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
Keywords: Carnitina palmitoïl-transferasa 1
Carnitine palmitoyltransferase I
Issue Date: 23-Dec-2019
Publisher: eLife Sciences
Abstract: 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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It is part of: eLife, 2019, vol. 8, p. e51063
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ISSN: 2050-084X
Appears in Collections:Articles publicats en revistes (Bioquímica i Fisiologia)

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