Cdc42 induces filopodia by promoting the formation of an IRSp53:Mena complex

@article{Krugmann2001Cdc42IF,
  title={Cdc42 induces filopodia by promoting the formation of an IRSp53:Mena complex},
  author={Sonja Krugmann and Ingrid Jordens and Kris Gevaert and Mariette H. E. Driessens and Joel Vandekerckhove and Alan Hall},
  journal={Current Biology},
  year={2001},
  volume={11},
  pages={1645-1655}
}
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The Cdc42 Effector IRSp53 Generates Filopodia by Coupling Membrane Protrusion with Actin Dynamics*
TLDR
It is proposed that IRSp53 generates filopodia by coupling membrane protrusion through its I-BAR domain with actin dynamics through SH3 domain binding partners, including N-WASP and Mena.
mDia1 and WAVE2 Proteins Interact Directly with IRSp53 in Filopodia and Are Involved in Filopodium Formation
TLDR
Findings suggest that mDia1 and WAVE2 are important Src homology 3 domain partners of IRSp53 in forming filopodia, which are dynamic actin-rich cell surface protrusions involved in cell migration, axon guidance, and wound healing.
Regulation of IRSp53-Dependent Filopodial Dynamics by Antagonism between 14-3-3 Binding and SH3-Mediated Localization
TLDR
This work provides an alternative model of how IRSp53 is recruited (and released) to carry out its functions at lamellipodia and filopodia, and does not conform to current views that the inverse-BAR domain or Cdc42 controlsIRSp53 localization.
Mechanism of IRSp53 inhibition and combinatorial activation by Cdc42 and downstream effectors
TLDR
Using a fluorescence reporter assay, it is shown that human IRSp53 adopts a closed inactive conformation that opens synergistically with the binding of human Cdc42 to the CRIB–PR and effector proteins, such as the tumor-promoting factor Eps8, to the SH3 domain.
LIN7 regulates the filopodium- and neurite-promoting activity of IRSp53
TLDR
Investigation of the role of the small scaffold protein LIN7 finds that formation of actin-filled protrusions in neuronal NSC34 cells and neurites in neuroblastoma N2A cells depends on motifs mediating the LIN7:IRSp53 association, and indicates that LIN7 is a novel regulator of IRSp53, and that the association of these proteins is required to promote the formation ofActin-dependent filopodia and neurite.
IRSp53 Mediates Podosome Formation via VASP in NIH-Src Cells
TLDR
It is found that the knockdown of IRSp53 by RNAi attenuates podosome formation and migration in Src-transformed NIH3T3 (NIH-Src) cells, and this data highlight the role ofIRSp53 as a linker of small GTPases to VASP for podosomes formation.
Dynamin1 Is a Novel Target for IRSp53 Protein and Works with Mammalian Enabled (Mena) Protein and Eps8 to Regulate Filopodial Dynamics*
TLDR
Dynin1 (Dyn1), the large guanosine triphosphatase, is an interacting partner of IRSp53 through pulldown and Förster resonance energy transfer analysis, and its role in filopodial formation is explored.
CDC42 switches IRSp53 from inhibition of actin growth to elongation by clustering of VASP
TLDR
It is shown that the membrane deforming and curvature sensing IRSp53 protein slows down actin filament barbed end growth, which results in spatial restriction of VASP filament elongation for initiation of filopodia during cell migration, invasion, and tissue repair.
I-BAR domains, IRSp53 and filopodium formation.
Structural basis of filopodia formation induced by the IRSp53/MIM homology domain of human IRSp53
TLDR
An expanded view of IRSp53 as an actin regulator that integrates scaffolding and effector functions is promoted, demonstrating that IMD‐mediated actin bundling is required for IRSp 53‐induced filopodia formation.
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TLDR
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