Adenomatous polyposis coli protein nucleates actin assembly and synergizes with the formin mDia1 |
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| Authors: | Kyoko Okada Francesca Bartolini Alexandra M Deaconescu James B Moseley Zvonimir Dogic Nikolaus Grigorieff Gregg G Gundersen Bruce L Goode |
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| Institution: | 1.Department of Biology, 2.Howard Hughes Medical Institute and Department of Biochemistry, and 3.Department of Physics, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454;4.Department of Pathology and Cell Biology, Columbia University, New York, NY 10032 |
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| Abstract: | The tumor suppressor protein adenomatous polyposis coli (APC) regulates cell protrusion and cell migration, processes that require the coordinated regulation of actin and microtubule dynamics. APC localizes in vivo to microtubule plus ends and actin-rich cortical protrusions, and has well-documented direct effects on microtubule dynamics. However, its potential effects on actin dynamics have remained elusive. Here, we show that the C-terminal “basic” domain of APC (APC-B) potently nucleates the formation of actin filaments in vitro and stimulates actin assembly in cells. Nucleation is achieved by a mechanism involving APC-B dimerization and recruitment of multiple actin monomers. Further, APC-B nucleation activity is synergistic with its in vivo binding partner, the formin mDia1. Together, APC-B and mDia1 overcome a dual cellular barrier to actin assembly imposed by profilin and capping protein. These observations define a new function for APC and support an emerging view of collaboration between distinct actin assembly–promoting factors with complementary activities. |
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