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

Marta Palomo-Guerrero, Rut Fadó, Maria Casas, Marta Pérez-Montero, Miguel Baena, Patrick O. Helmer, José Luis Domínguez, Aina Roig, Dolors Serra, Heiko Hayen, Harald Stenmark, Camilla Raiborg, Núria Casals

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    1 Scopus citations

    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.

    Original languageEnglish (US)
    Article numbere51063
    JournaleLife
    Volume8
    DOIs
    StatePublished - Dec 2019

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Immunology and Microbiology(all)
    • Biochemistry, Genetics and Molecular Biology(all)

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    Palomo-Guerrero, M., Fadó, R., Casas, M., Pérez-Montero, M., Baena, M., Helmer, P. O., Domínguez, J. L., Roig, A., Serra, D., Hayen, H., Stenmark, H., Raiborg, C., & Casals, N. (2019). Sensing of nutrients by CPT1C regulates late endosome/lysosome anterograde transport and axon growth. eLife, 8, [e51063]. https://doi.org/10.7554/eLife.51063