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
Elifejournal_title
eLifeauthors
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 Ndoi
10.7554/eLife.51063subject
Has Abstractpub_date
2019-12-23 00:00:00issn
2050-084Xpii
51063journal_volume
8pub_type
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