Cdk5 and GSK3β inhibit Fast Endophilin-Mediated Endocytosis

Autor: Konstantinos Thalassinos, Emmanuel Boucrot, Shaan Subramaniam, Sara Carrillo Roas, Alessandra Casamento, Kira Schützenhofer, Denis Martinvalet, Josef T. Kittler, Laura Chan Wah Hak, Antonio P A Ferreira, James Panambalana, Els F. Halff, Kieran McGourty
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
medicine.medical_treatment
Endocytic cycle
General Physics and Astronomy
Muscle Proteins
Membrane trafficking
Inbred C57BL
Adaptor Proteins
Signal Transducing
Animals
Cells
Cultured
Clathrin
Cyclin-Dependent Kinase 5
Dynamin I
Endocytosis
Gene Expression Regulation
Glycogen Synthase Kinase 3 beta
HEK293 Cells
HeLa Cells
Hippocampus
Humans
Mice
Inbred C57BL
Neurons
Protein Binding
RNA Interference
Mice
0302 clinical medicine
Membrane fission
Receptor
0303 health sciences
Multidisciplinary
Cultured
biology
Chemistry
Kinase
Adaptor Proteins
3. Good health
Cell biology
Cells
Science
Dynein
Transport carrier
General Biochemistry
Genetics and Molecular Biology
Article
03 medical and health sciences
medicine
Growth cone
030304 developmental biology
Growth factor
Cyclin-dependent kinase 5
Plexin
Signal Transducing
General Chemistry
030104 developmental biology
nervous system
biology.protein
030217 neurology & neurosurgery
Zdroj: Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021)
Nature Communications
DOI: 10.1101/2020.04.11.036863
Popis: 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.
Endocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Here, the authors show that Cdk5 and GSK3β are negative regulators of fast Endophilin-mediated endocytosis (FEME).
Databáze: OpenAIRE
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