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

Authors :
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
Source :
eLife, Vol 8 (2019)
Publication Year :
2019
Publisher :
eLife Sciences Publications Ltd, 2019.

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.

Details

Language :
English
ISSN :
2050084X
Volume :
8
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.3271027ebcbb4e948ef1a81bd8c4e174
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.51063