Sensing of nutrients by CPT1C regulates late endosome/lysosome anterograde transport and axon growth
Author
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
Publication date
2019ISSN
2050-084X
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.
Document Type
Article
Document version
Accepted version
Language
English
Subject (CDU)
61 - Medical sciences
Keywords
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
Pages
26
Publisher
eLife Sciences Publications
Collection
8;
Is part of
eLife
Citation
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.
Grant agreement number
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
This item appears in the following Collection(s)
- Ciències de la Salut [740]
Rights
© 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.
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/