Cdk5 and GSK3β inhibit fast endophilin-mediated endocytosis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33893293.
- Also identified by DOI 10.1038/s41467-021-22603-4 and PMC identifier 8065113.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Adaptor Proteins, Signal Transducing
- Cyclin-Dependent Kinase 5
- Endocytosis
- Glycogen Synthase Kinase 3 beta