Casein kinase 1δ/ε regulates clathrin‐ and actin‐mediated endocytosis

• DOI: 10.1096/fasebj.27.1_supplement.553.25
• Publication Date: 2021-06-16T10:27:52Z
• Authors: Yutian Connie Peng; Alexandre Grassart; Rebecca Lu; Alphée Michelot; Catherine C. L. Wong; John Yate; Georjana Barnes; David G Drubin
• Keywords: 0301 basic medicine; 03 medical and health sciences

While much has been learned about the mechanisms by which clathrin‐coated vesicles are formed during endocytosis, much less is known about how their formation is regulated. Here, we investigate the role of protein phosphorylation in regulation of clathrin‐mediated endocytosis. We found that in both budding yeast and mammalian cells the casein kinase 1δ/ε, Hrr25, associates with and regulates the endocytic machinery. In budding yeast, Hrr25 is recruited to endocytic patches early in the pathway by the C‐terminus of the yeast Eps15‐like protein, Ede1, where it phosphorylates Ede1 and several other endocytic proteins. An analog‐sensitive allele was created and used to show that Hrr25 kinase activity is required for the kinase's recruitment to endocytic sites. Loss of the kinase activity impairs initiation of endocytosis and causes abnormal patch dynamics. Furthermore, our results in mammalian cells provide evidence for conservation of casein kinase 1δ/ε functions in more complex organisms. Ongoing studies are aimed at elucidating the detailed mechanisms and specific in vivo phosphorylation targets underlying Hrr25's regulatory functions in endocytosis.