Date
2021
Abstract
Endocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Fast Endophilin-mediated endocytosis, FEME, is not constitutively active but triggered upon receptor activation. High levels of growth factors induce spontaneous FEME, which can be suppressed upon serum starvation. This suggested a role for protein kinases in this growth factor receptor-mediated regulation. Using chemical and genetic inhibition, we find that Cdk5 and GSK3β are negative regulators of FEME. They antagonize the binding of Endophilin to Dynamin-1 and to CRMP4, a Plexin A1 adaptor. This control is required for proper axon elongation, branching and growth cone formation in hippocampal neurons. The kinases also block the recruitment of Dynein onto FEME carriers by Bin1. As GSK3β binds to Endophilin, it imposes a local regulation of FEME. Thus, Cdk5 and GSK3β are key regulators of FEME, licensing cells for rapid uptake by the pathway only when their activity is low.
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Description
peer-reviewed
Publisher
Nature Publishing Group
Citation
Nature Communications;12, 2424
Collections
Chemical Sciences
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McGourty_2021_Cdk5.pdf
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Keywords
Endophilin, Endocytosis
ULRR Identifiers
https://researchrepository.ul.ie/handle/10344/10140
 https://doi.org/10.34961/2572
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Funding Information
European Research Council (ERC), Wellcome Trust
Sustainable Development Goals
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Type
Article
Rights
https://creativecommons.org/licenses/by-nc-sa/1.0/
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