Published 28 August 2006. doi:10.1083/jcb.1745iti3
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 174, Number 5, 608-608
Formin localization
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Only autoinhibition (top) prevents FRL formin from locating to the plasma membrane.
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Interaction between the NH2- and COOH-terminal regions of formin proteins serves two autoinhibitory functions simultaneously, report Seth et al. on page 701. The first, more familiar function is to block actin nucleation by the COOH-terminal region. More novel is the second function: preventing localization of the protein to the plasma membrane, normally mediated by the NH2-terminal domain.
The Diaphanous-related formins nucleate unbranched actin filaments during cytoskeletal remodeling. In the case of mDia1 formin, this nucleation activity is autoinhibited by interaction between the NH2 and COOH termini of the protein. Seth et al. show that the formin family member FRL is autoinhibited by the same mechanism.
Blocking autoinhibition via mutation had a second consequence: FRL moved from the cytoplasm to the plasma membrane. This plasma membrane localization was dependent on the NH2-terminal domain and was enhanced by interaction with the activated form of the RhoGTPase Cdc42.
A similar membrane localization activity was detected in the NH2-terminal region of mDia1. Localization of both proteins had a GTPase-dependent and -independent component, suggesting a still undiscovered membrane-associated formin ligand.
Given the similarities between the two formin proteins, Seth et al. hypothesize that this mutual autoinhibitory pattern involving both activity and localization will be characteristic of the formin family—and may be more broadly found in autoinhibitory proteins in general. Moreover, unique interactions between different formin family members and Rho GTPases likely give each actin nucleator a distinct role in cytoskeletal remodeling, as has been seen with yeast formins. 
Rabiya S. Tuma
rabiya{at}nasw.org
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Autoinhibition regulates cellular localization and actin assembly activity of the diaphanous-related formins FRL and mDia1
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