Adenomatous polyposis coli protein nucleates actin assembly and synergizes with the formin mDia1.
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.
Okada
Kyoko
K
Department of Biology, Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02454, USA.
Bartolini
Francesca
F
Deaconescu
Alexandra M
AM
Moseley
James B
JB
Dogic
Zvonimir
Z
Grigorieff
Nikolaus
N
Gundersen
Gregg G
GG
Goode
Bruce L
BL
D051344:Actin Capping Proteins; D000199:Actins / Q000378:metabolism*; D025601:Adenomatous Polyposis Coli Protein / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D005326:Fetal Proteins / Q000502:physiology; D000080865:Formins; D051379:Mice; D008840:Microfilament Proteins / Q000502:physiology; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000502:physiology; D051304:Profilins; D055503:Protein Multimerization; D021381:Protein Transport
D051344:Actin Capping Proteins; D000199:Actins; D025601:Adenomatous Polyposis Coli Protein; D002352:Carrier Proteins; C491464:Diap1 protein, mouse; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D051304:Profilins