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Published on: May 12, 2018
WIP regulates N-WASP-mediated actin polymerization and filopodium formation.
N Martinez-Quiles1, R Rohatgi, I M Antón
1Department of Pediatrics, Division of Immunology, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature Cell Biology
|May 2, 2001
Summary
WASP-interacting protein (WIP) and neural Wiskott-Aldrich-syndrome protein (N-WASP) form a functional unit that regulates actin polymerization and filopodia formation. This interaction is crucial for cell shape changes and pathogen invasion.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Filopodia formation is regulated by the small GTPase Cdc42 and neural Wiskott-Aldrich-syndrome protein (N-WASP).
- The precise role of WASP-interacting protein (WIP) in this process was not fully understood.
Purpose of the Study:
- To investigate the interaction between WIP and N-WASP in the context of filopodium formation.
- To elucidate the functional role of WIP in actin dynamics and cell structure.
Main Methods:
- Direct interaction assays between WIP, N-WASP, and actin.
- Microinjection of WIP and anti-N-WASP antibodies into NIH 3T3 fibroblasts.
- Analysis of filopodia induction by various stimuli, including bradykinin and a constitutively active Cdc42 mutant.
Main Results:
- WIP directly interacts with N-WASP and actin, forming a complex.
- WIP retards Arp2/3 complex-mediated actin polymerization activated by N-WASP/Cdc42 and stabilizes actin filaments.
- Microinjection of WIP induced filopodia, an effect blocked by anti-N-WASP antibodies.
- Inhibition of WIP blocked filopodia induction by bradykinin, Cdc42(V12), and N-WASP.
Conclusions:
- WIP and N-WASP function as a unit in filopodium formation.
- This WIP-N-WASP complex plays a critical role in regulating actin dynamics for cell structure and motility.
- The findings are consistent with the known roles of WIP and N-WASP in actin-tail formation during pathogen infection.
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