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Published on: June 3, 2021
Dia-interacting protein modulates formin-mediated actin assembly at the cell cortex
Kathryn M Eisenmann1, Elizabeth S Harris, Susan M Kitchen
1Laboratory of Cell Structure and Signal Integration, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Dia-interacting protein (DIP) controls actin assembly by interacting with formins and Arp2/3. DIP specifically inhibits mDia2-mediated filament assembly and induces membrane blebbing, highlighting its role in actin dynamics and cell shape.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Mammalian diaphanous (mDia)-related formins and N-WASP-activated Arp2/3 complex are key regulators of filamentous actin assembly.
- Dia-interacting protein (DIP) binds to mDia formins and N-WASP via its SH3 domain and proline-rich regions.
Purpose of the Study:
- Investigate the interaction between DIP's leucine-rich region (LRR) and the mDia FH2 domain.
- Determine DIP's role in regulating actin filament nucleation, elongation, and bundling.
- Clarify DIP's function in filopodia formation and membrane blebbing.
Main Methods:
- In vitro binding assays to study DIP-mDia interactions.
- Analysis of actin filament assembly and bundling.
- Cell-based assays to observe effects of DIP expression on filopodia and membrane blebbing.
Main Results:
- DIP's LRR binds to the mDia FH2 domain, regulating actin nucleation, elongation, and bundling.
- DIP binding to mDia2 is controlled by the Rho-GTPase autoinhibitory mechanism.
- DIP inhibits mDia2-dependent actin filament assembly and bundling in vitro.
- DIP expression interferes with filopodia formation and induces mDia2-dependent membrane blebbing.
Conclusions:
- DIP plays a crucial role in controlling both branched and non-branched actin-filament assembly.
- DIP regulates actin assembly mediated by Diaphanous-related formins and Arp2/3 activators.
- DIP's ability to induce blebbing suggests a role for mDia2 in cortical actin assembly for plasma-membrane integrity.
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