Putting a new twist on actin: ADF/cofilins modulate actin dynamics

doi:10.1016/S0962-8924(99)01619-0

Trends in Cell Biology

Volume 9, Issue 9, 1 September 1999, Pages 364-370

https://doi.org/10.1016/S0962-8924(99)01619-0 Get rights and content

Abstract

The actin-depolymerizing factor (ADF)/cofilins are a family of essential actin regulatory proteins, ubiquitous among eukaryotes, that enhance the turnover of actin by regulating the rate constants of polymerization and depolymerization at filament ends, changing the twist of the filament and severing actin filaments. Genetic and cell-biological studies have shown that an ADF/cofilin is required to drive the high turnover of the actin cytoskeleton observed in vivo. The activity of ADF/cofilin is regulated by a variety of mechanisms, including specific phosphorylation and dephosphorylation. This review addresses aspects of ADF/cofilin structure, dynamics, regulation and function.

Section snippets

Structure of the ADF/cofilins

There are over 28 members of the AC protein family distributed across the complete spectrum of eukaryotic organisms. Although they share many features in common, some comparative biochemical studies have revealed functional differences that suggest that AC proteins might have evolved to serve different roles in particular organisms or cell types. This idea is borne out by comparison of the primary, secondary and tertiary structures of AC proteins. For example, phylogenetic tree analysis reveals

ADF/cofilins enhances dynamics of actin assembly

The unique effects that AC proteins have on actin filament structure appear to explain many of their functional properties as well. Although it was known for some time that AC depolymerized actin filaments, the mechanism it employs remained elusive. Carlier and colleagues were the first to quantify a unique feature of the mechanism: AC increases the dissociation rate constant for actin subunits from the pointed end of the filament²³. In addition, AC has been shown by light²⁴ and electron

Mechanisms regulating ADF/cofilin activity

Cells integrate a large number of environmental signals to regulate the proper spatial and temporal patterns of actin dynamics required for many different cellular processes. The activity of AC family members is regulated through expression and by many posttranslational mechanisms.

In vivo functions of ADF/cofilin: evidence from genetic model organisms

As the biochemical properties of AC family members suggest, they mediate several intracellular events that require rapid actin filament dynamics. The strongest evidence for the in vivo function of the AC family has been provided from studies in model organisms in which the genes encoding ACs have been mutated and the resultant mutant phenotypes characterized. Important observations are that null and strong loss-of-function mutations in the AC genes cause lethality in yeast13, 58, 59, fruit fly⁶⁰

Concluding remarks

As a common downstream target of all of the Rho family GTPases, AC protein regulation is crucial to actin reorganization. The GTPases that organize the filamentous actin into filopodial bundles (Cdc42), lamellipodial dendritic brush (Rac) or actin stress fibres (Rho) have other unique molecular targets recruited for membrane binding and filament crosslinking or bundling. In addition, regulation of AC by phosphoinositides, competitive binding with tropomyosin, pointed-end capping and other

Acknowledgements

We thank our colleagues who shared unpublished data with us. We apologize to all those who have made substantial contributions to the field but whose work is not cited here owing to lack of space. Our work covered in this review was supported by grants GM35126 and GM54004 (J. R. B.) from the NIH, 96010660 (A. M.) from the American Heart Association and MCB-9728762 (G. M. Benian and S. O.) from the NSF.

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Trends in Cell Biology

ReviewPutting a new twist on actin: ADF/cofilins modulate actin dynamics

Abstract

Section snippets

Structure of the ADF/cofilins

ADF/cofilins enhances dynamics of actin assembly

Mechanisms regulating ADF/cofilin activity

In vivo functions of ADF/cofilin: evidence from genetic model organisms

Concluding remarks

Acknowledgements

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Review
Putting a new twist on actin: ADF/cofilins modulate actin dynamics