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

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.

journal_name

Elife

journal_title

eLife

authors

Palomo-Guerrero M,Fadó R,Casas M,Pérez-Montero M,Baena M,Helmer PO,Domínguez JL,Roig A,Serra D,Hayen H,Stenmark H,Raiborg C,Casals N

doi

10.7554/eLife.51063

subject

Has Abstract

pub_date

2019-12-23 00:00:00

issn

2050-084X

pii

51063

journal_volume

8

pub_type

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