Letter abstract
Nature Cell Biology 7, 246 - 254 (2005)
Published online: 13 February 2005 | doi:10.1038/ncb1229
Phosphoregulation of Arp2/3-dependent actin assembly during receptor-mediated endocytosis
Jiro Toshima1, Junko Y. Toshima1, Adam C. Martin1 & David G. Drubin1
In both yeast and mammals, endocytic internalization is accompanied by a transient burst of actin polymerization1, 2. The yeast protein kinases Prk1p and Ark1p, which are related to the mammalian proteins GAK and AAK1, are key regulators of this process3, 4, 5, 6. However, the molecular mechanism(s) by which they regulate actin assembly at endocytic sites have not yet been determined. The Eps15-like yeast protein Pan1p is a Prk1p substrate that is essential for endocytic internalization and for proper actin organization7, 8, 9. Pan1p is an Arp2/3 activator and here we show that this activity is dependent on F-actin binding. Mutation of all 15 Prk1p-targeted threonines in Pan1p to alanines mimicked the ark1
prk1 phenotype, demonstrating that Pan1p is a key Prk1p target in vivo. Moreover, phosphorylation by Prk1p inhibited the ability of Pan1p to bind to F-actin and to activate the Arp2/3 complex, thereby identifying the endocytic phosphoregulation mechanism of Prk1p. We conclude that Prk1p phosphorylation of Pan1p shuts off Arp2/3-mediated actin polymerization on endocytic vesicles, allowing them to fuse with endosomes.
- Department of Molecular and Cell Biology, 16 Barker Hall, University of California, Berkeley, CA 94720-3202, USA.
Correspondence to: David G. Drubin1 e-mail: drubin@socrates.berkeley.edu
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