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Dynamics of filopodia tip complexes

  • Author(s): Cheng, Karen
  • Advisor(s): Mullins, Roland D
  • et al.
Abstract

The shape of many eukaryotic cells depends on the actin cytoskeleton, and changes in actin assembly dynamics underlie many changes in cell shape. Ena/VASP-family actin polymerases, for example, modulate cell shape by locally accelerating actin filament assembly and slowing filament capping. When concentrated into discrete foci at the leading edge, VASP promotes filopodia assembly, and forms part of a poorly understood molecular complex that remains associated with growing filopodia tips. Here we identify precursors of this filopodia tip complex in migrating B16F1 cells: small leading-edge clusters of the adaptor protein lamellipodin (Lpd) which subsequently recruit VASP and initiate filopodia formation. Dimerization, membrane association, and VASP binding are all required for lamellipodin to incorporate into filopodia tip complexes, and over-expression of monomeric, membrane-targeted lamellipodin mutants disrupts tip complex assembly. Once formed, VASP and lamellipodin-containing tip complexes grow by fusing with each other, but their growth is limited by a size-dependent, dynamic instability. Our results demonstrate that assembly and disassembly dynamics of filopodia tip complexes are determined, in part, by a network of multivalent interactions between Ena/VASP proteins, EVH1 ligands, and actin filaments.

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