Article Alert: Fast Endophilin-Mediated Endocytosis: Regulation by Cdk5 and GSK3β

11-Oct-2022

Fast Endophilin-Mediated Endocytosis (FEME) is an inducible clathrin-independent endocytic mechanism responsible for particular functions or uptake of specific cargoes. While the component framework of carrier production has been described, little was known about how the process is regulated. In a recent study, Ferreira et al. made a major contribution by discovering that the protein kinases Cdk5 and GSK3β play key roles in the negative regulation of FEME (1). The authors used both genetic and chemical approaches to show that disruption of these kinases results in FEME activation. They determined that these kinases exert their effects on multiple steps of the pathway affecting cargo disposition, membrane dynamics, and microtubule-directed carrier transport through inhibition of CRMP4 and dynamin-1 binding to endophilin as well as blockage of Bin-1-dependent recruitment of dynein to FEME carriers. Functionally, the researchers found that the actions of Cdk5 and GSK3β are necessary for normal growth cone and axonal development in mouse hippocampal neurons, emphasizing the role of FEME in orchestrating synaptic connectivity in the vertebrate central nervous system.

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