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J Biol Chem, Vol. 274, Issue 6, 3257-3260, February 5, 1999

COMMUNICATION
The Interaction of Epsin and Eps15 with the Clathrin Adaptor AP-2 Is Inhibited by Mitotic Phosphorylation and Enhanced by Stimulation-dependent Dephosphorylation in Nerve Terminals

Hong ChenDagger , Vladimir I. SlepnevDagger , Pier Paolo Di Fiore§, and Pietro De CamilliDagger

From the Dagger  Howard Hughes Medical Institute and Department of Cell Biology, Yale University School of Medicine, New Haven Connecticut 06510, the § Department of Experimental Oncology, European Institute of Oncology, Milan 20141, Italy, and the  Istituto di Microbiologia, Universitá di Bari, Bari 70124, Italy

Clathrin-mediated endocytosis was shown to be arrested in mitosis due to a block in the invagination of clathrin-coated pits. A Xenopus mitotic phosphoprotein, MP90, is very similar to an abundant mammalian nerve terminal protein, epsin, which binds the Eps15 homology (EH) domain of Eps15 and the alpha -adaptin subunit of the clathrin adaptor AP-2. We show here that both rat epsin and Eps15 are mitotic phosphoproteins and that their mitotic phosphorylation inhibits binding to the appendage domain of alpha -adaptin. Both epsin and Eps15, like other cytosolic components of the synaptic vesicle endocytic machinery, undergo constitutive phosphorylation and depolarization-dependent dephosphorylation in nerve terminals. Furthermore, their binding to AP-2 in brain extracts is enhanced by dephosphorylation. Epsin together with Eps15 was proposed to assist the clathrin coat in its dynamic rearrangements during the invagination/fission reactions. Their mitotic phosphorylation may be one of the mechanisms by which the invagination of clathrin-coated pits is blocked in mitosis and their stimulation-dependent dephosphorylation at synapses may contribute to the compensatory burst of endocytosis after a secretory stimulus.


Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.



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