WH2 and proline‐rich domains of WASP‐family proteins collaborate to accelerate actin filament elongation

• Peter Bieling ^[1] ; Scott D Hansen ^[2] ; Orkun Akin ^[3] ; Tai‐De Li ^[4] ; Carl C Hayden ^[5] ; Daniel A Fletcher ^[6] ; R Dyche Mullins ^[7]
  1. [1] 1 Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute University of California San Francisco CA USA; 2 Department of Bioengineering & Biophysics Program University of California Berkeley CA USA; 3 Chan Zuckerberg Biohub San Francisco CA USA; 6Present address: Department of Systemic Cell Biology Max Planck Institute of Molecular Physiology Dortmund Germany
  2. [2] 1 Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute University of California San Francisco CA USA; 7Present address: Department of Chemistry and Biochemistry University of Oregon Eugene OR USA
  3. [3] 1 Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute University of California San Francisco CA USA; 8Present address: Department of Biological Chemistry University of California Los Angeles CA USA
  4. [4] 2 Department of Bioengineering & Biophysics Program University of California Berkeley CA USA; 3 Chan Zuckerberg Biohub San Francisco CA USA; 4 Biological Systems & Engineering Division Lawrence Berkeley National Laboratory Berkeley CA USA; 9Present address: Advanced Science Research Center City University of New York New York NY USA
  5. [5] 5 Sandia National Laboratories Livermore CA USA; 10Present address: Department of Biomedical Engineering The University of Texas at Austin Austin TX USA
  6. [6] 2 Department of Bioengineering & Biophysics Program University of California Berkeley CA USA; 3 Chan Zuckerberg Biohub San Francisco CA USA; 4 Biological Systems & Engineering Division Lawrence Berkeley National Laboratory Berkeley CA USA
  7. [7] 1 Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute University of California San Francisco CA USA

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 37, Nº. 1, 2018, págs. 102-121
• Idioma: inglés
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  • WASP‐family proteins are known to promote assembly of branched actin networks by stimulating the filament‐nucleating activity of the Arp2/3 complex. Here, we show that WASP‐family proteins also function as polymerases that accelerate elongation of uncapped actin filaments. When clustered on a surface, WASP‐family proteins can drive branched actin networks to grow much faster than they could by direct incorporation of soluble monomers. This polymerase activity arises from the coordinated action of two regulatory sequences: (i) a WASP homology 2 (WH2) domain that binds actin, and (ii) a proline‐rich sequence that binds profilin–actin complexes. In the absence of profilin, WH2 domains are sufficient to accelerate filament elongation, but in the presence of profilin, proline‐rich sequences are required to support polymerase activity by (i) bringing polymerization‐competent actin monomers in proximity to growing filament ends, and (ii) promoting shuttling of actin monomers from profilin–actin complexes onto nearby WH2 domains. Unoccupied WH2 domains transiently associate with free filament ends, preventing their growth and dynamically tethering the branched actin network to the WASP‐family proteins that create it. Collaboration between WH2 and proline‐rich sequences thus strikes a balance between filament growth and tethering. Our work expands the number of critical roles that WASP‐family proteins play in the assembly of branched actin networks to at least three: (i) promoting dendritic nucleation; (ii) linking actin networks to membranes; and (iii) accelerating filament elongation.