Sensing of nutrients by CPT1C regulates late endosome/lysosome anterograde transport and axon growth
Autor/a
Palomo Guerrero, Marta
Fadó Andrés, Rut
Pérez-Montero, Marta
Baena, Miguel
Helmer, Patrick O.
Domínguez, José Luis
Roig, Aina
Serra, Dolors
Hayen, Heiko
Stenmark, Harald
Raiborg, Camilla
Casals i Farré, Núria
Fecha de publicación
2019ISSN
2050-084X
Resumen
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.
Tipo de documento
Artículo
Versión del documento
Versión aceptada
Lengua
English
Materias (CDU)
61 - Medicina
Palabras clave
Lisosomes
Àcids grassos
Glucosa
Neurones
Axons
Citologia
Neurociències
Ratolins
Lisosomas
Ácidos grasos
Glucosa
Neuronas
Axiomas
Citología
Neurociencias
Ratones
Lysosomes
Fatty acids
Glucose
Neurons
Axons
Cytology
Neurosciences
Mice
Páginas
26
Publicado por
eLife Sciences Publications
Colección
8;
Publicado en
eLife
Citación
Palomo-Guerrero, Marta; Fadó Andrés, Rut; Casas, Maria [et al.]. Sensing of nutrients by CPT1C regulates late endosome/lysosome anterograde transport and axon growth. eLife, 2019, 8, e51063. Disponible en: <https://elifesciences.org/articles/51063>. Fecha de acceso: 27 may. 2020. DOI: 10.7554/eLife.51063.
Número del acuerdo de la subvención
info:eu-repo/grantAgreement/ES/2PE/SAF2017-83813-C3-1-R
info:eu-repo/grantAgreement/ES/1PE/SAF2014-52223-C2-2-R
info:eu-repo/grantAgreement/ES/2PE/SAF2017-82813-C3-3R
info:eu-repo/grantAgreement/ES/1PE/SAF2014-52223-C2-1-R
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Derechos
© Palomo-Guerrero et. al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Excepto si se señala otra cosa, la licencia del ítem se describe como https://creativecommons.org/licenses/by/4.0/